Alpha-carbon chiral phosphine compounds and methods for their preparation

Abstract

The application belongs to the technical field of asymmetric catalytic synthesis, and particularly relates to an alpha-carbon chiral phosphine compound and a preparation method thereof. In a protective gas atmosphere, an asymmetric boron protonation reaction is carried out on a dienyl phosphine oxide compound shown in a structure of formula II, pinacol borate, a copper (I) catalyst, a chiral ligand, an organic alkaline compound and a proton additive in a polar organic solvent to obtain an alpha-carbon chiral phosphine compound shown in a structure of formula I; the chiral ligand is a cyclic phosphine ligand (S, S)-Ph-BPE or a cyclic phosphine ligand (R, R)-Ph-BPE. The preparation method provided by the application can synthesize the alpha-carbon chiral phosphine compound shown in the structure of formula I with high yield and excellent enantioselectivity, the synthesis method is simple and low in cost, and the alpha-carbon chiral phosphine compound can be further converted into a new optically active product.

Description

Technical Field

[0001] This invention belongs to the field of asymmetric catalytic synthesis technology, specifically relating to an α-carbon chiral phosphine compound and its preparation method. Background Technology

[0002] Chiral phosphine compounds have important applications in organic synthesis, medicinal chemistry, and materials science. They play a crucial role in the synthesis of chiral compounds as ligands in organocatalysts or transition metal asymmetric catalysis. However, current synthesis methods primarily rely on stoichiometric chiral auxiliary reagents or chiral resolution methods. The limited variety, large quantities, and narrow applications of effective chiral reagents, coupled with the complexity and unstable resolution effects of chiral resolution methods, significantly restrict the synthesis and application of diverse and multifunctional chiral phosphine compounds.

[0003] The synthesis of chiral phosphine compounds using asymmetric catalysis offers advantages such as being environmentally friendly, having tunable catalytic systems, and yielding various chiral types and structural diversity. Asymmetric boration of phosphine compounds containing unsaturated bonds using transition metal catalysis is an effective method for constructing chiral centers. For example, phosphine compounds containing carbon-carbon double bonds can be synthesized into β-, γ-, or δ-carbon chiral phosphine compounds via asymmetric hydroboration under copper or rhodium catalysis.

[0004] However, the above-mentioned asymmetric borylation reaction method cannot effectively synthesize α-carbon chiral phosphine compounds. Summary of the Invention

[0005] The purpose of this invention is to provide an α-carbon chiral phosphine compound and its preparation method. This invention uses a copper (I) catalyst as a catalyst to synthesize an α-carbon chiral phosphine compound with the structure shown in Formula I in high yield and with high enantioselectivity through an asymmetric boron protonation reaction. The synthesis method is simple and low in cost, and the α-carbon chiral phosphine compound can be further converted into new optically active products.

[0006] To achieve the above objectives, the present invention provides the following technical solution:

[0007] This invention provides an α-carbon chiral phosphine compound having the structure shown in Formula I:

[0008]

[0009] In Formula I, R 1 C 1～8 alkyl, C 3～8 cycloalkyl, C 1～8 The alkoxy, amino, aryl, or substituted aryl groups, wherein the R 1 The substituents on the aryl group are fluorine, chlorine, bromine, nitro, trifluoromethyl, C1～4 at least one of alkyl and C 1～4 at least one of alkyl and C

[0010] R 2 is C 1～4 alkyl, aryl, substituted aryl or thienyl, the substituent on the substituted aryl in R 2 is at least one of fluorine, chlorine, bromine, iodine, nitro, trifluoromethyl, C 1～4 alkyl, C 1～4 alkoxy, C 1～4 substituted alkoxy, ester and cyano.

[0011] Preferably, R 1 is phenyl, MeO-*, EtO-*, or

[0012] R 2 is phenyl, naphthyl,

[0013] Preferably, the α-carbon chiral phosphine compound has any one of the following structures:

[0014]

[0015] The present application provides a preparation method of the α-carbon chiral phosphine compound as described in the above technical solution, comprising the following steps:

[0016] In a protective gas atmosphere, the allene phosphine oxide compound shown in the structure of formula II, pinacol borate, copper (I) catalyst, chiral ligand, organic alkaline compound, proton additive are subjected to asymmetric boron protonation reaction in a polar organic solvent to obtain the α-carbon chiral phosphine compound; the chiral ligand is a cyclic phosphine ligand (S, S)-Ph-BPE or a cyclic phosphine ligand (R, R)-Ph-BPE.

[0017]

[0018] Preferably, the copper (I) catalyst is one or more of CuCl, CuBr, CuI, CuOAc, CuTc and Cu (CH3CN) 4PF6.

[0019] Preferably, the temperature of the asymmetric boron protonation reaction is -30 to -60℃.

[0020] Preferably, the organic alkaline compound is sodium tert-butoxide.

[0021] Preferably, the proton additive is methanol.

[0022] Preferably, the molar ratio of the allene phosphine oxide compound of the structure shown in Formula II to the pinacol borate is 1: (1-2) ;

[0023] The molar ratio of the allene phosphine oxide compound of the structure shown in Formula II to the copper (I) catalyst is 1:0.05;

[0024] The molar ratio of the allene phosphine oxide compound of the structure shown in Formula II to the chiral ligand is 1:0.06;

[0025] The molar ratio of the allene phosphine oxide compound of the structure shown in Formula II to the proton additive is 1:2;

[0026] The molar ratio of the allene phosphine oxide compound of the structure shown in Formula II to the organic basic compound is 1:0.2.

[0027] Preferably, the copper (I) catalyst is CuOAc; the temperature of the asymmetric boron protonation reaction is -55℃.

[0028] The present application provides an α-carbon chiral phosphine compound, having the structure shown in Formula I, wherein R 1 is a C 1～8 alkyl group, a C 3～8 cycloalkyl group, a C 1～8 alkoxy group, an amine group, an aryl group or a substituted aryl group, wherein the substituent on the substituted aryl group in R 1 is at least one of fluorine, chlorine, bromine, nitro, trifluoromethyl, a C 1～4 alkyl group and a C 1～4 alkoxy group; R 2 is a C 1～4 alkyl group, an aryl group, a substituted aryl group or a thiophene group, wherein the substituent on the substituted aryl group in R 2 is at least one of fluorine, chlorine, bromine, iodine, nitro, trifluoromethyl, a C 1～4 alkyl group, a C 1～4 alkoxy group, a C 1～4 substituted alkoxy group, an ester group and a cyano group. The boron-functionalized chiral allyl phosphine oxide compound of the structure shown in Formula I provided by the present application can be further converted into new optically active products, expanding the synthesis method of chiral phosphine compounds and broadening its application in the synthesis of chiral compounds.

[0029] The application provides a preparation method of the alpha-carbon chiral phosphine compound, and the method comprises the following steps: performing asymmetric boron protonation reaction on a allelic phosphine oxide compound shown in a structure of formula II, pinacol borate (B2pin2), a copper (I) catalyst, a chiral ligand, an organic alkaline compound and a proton additive in a polar organic solvent in a protective gas atmosphere to obtain the alpha-carbon chiral phosphine compound; and the chiral ligand is a cyclic phosphine ligand (S, S)-Ph-BPE or a cyclic phosphine ligand (R, R)-Ph-BPE. According to the preparation method, the copper (I) complex is generated in situ from the chiral ligand and the copper (I) catalyst under the action of the organic alkaline compound, then the active copper boron complex is generated by the transmetalation reaction of the copper (I) complex and B2pin2, the allyl copper intermediate is formed by the cupration reaction of the allelic phosphine oxide compound shown in the structure of formula II and the copper boron complex, finally, the target product alpha-carbon chiral phosphine compound is obtained by the protonation of the allyl copper intermediate and the proton additive, and the copper (I) catalyst is regenerated. According to the preparation method, the electron-withdrawing property of the phosphine oxide group induces the regioselectivity in the allelic cupration process, and the allyl copper intermediate is obtained, which is a key step for realizing high enantioselectivity according to the application. According to the preparation method, the alpha-carbon chiral phosphine compound shown in the structure of formula I can be synthesized at a high yield and excellent enantioselectivity. BRIEF DESCRIPTION OF DRAWINGS

[0030] Figure 1 A single crystal diffraction structure of compound 6 in the application example. 1 H NMR spectrum.

[0031] Figure 2 A single crystal diffraction structure of compound 6 in the application example. DETAILED DESCRIPTION

[0032] The application provides an alpha-carbon chiral phosphine compound, which has a structure shown in formula I.

[0033]

[0034] In formula I, the R 1 is C 1～8 alkyl, C 3～8 cycloalkyl, C 1～8 alkoxy, an amine group, an aryl group or a substituted aryl group, and the substituent group on the substituted aryl group in the R 1 is at least one of fluorine, chlorine, bromine, a nitro group, a trifluoromethyl group, C 1～4 alkyl and C 1～4 alkoxy.

[0035] The R 2 is C 1～4 alkyl, an aryl group, a substituted aryl group or a thiophene group, and the R2 substituents on the substituted aryl group in the formula (I) are at least one of fluorine, chlorine, bromine, iodine, nitro, trifluoromethyl, C 1～4 substituents on the substituted aryl group in the formula (I) are at least one of fluorine, chlorine, bromine, iodine, nitro, trifluoromethyl, C 1～4 substituents on the substituted aryl group in the formula (I) are at least one of fluorine, chlorine, bromine, iodine, nitro, trifluoromethyl, C 1～4 substituents on the substituted aryl group in the formula (I) are at least one of fluorine, chlorine, bromine, iodine, nitro, trifluoromethyl, C

[0036] In the present application, the R 1 preferably is phenyl, MeO-*, EtO-*, or

[0037] In the present application, the R 2 preferably is phenyl, naphthyl,

[0038] In the present application, the α-carbon chiral phosphine compound preferably has any one of the following structures:

[0039]

[0040] The present application provides a preparation method of the α-carbon chiral phosphine compound as described in the above technical solution, comprising the following steps:

[0041] under a protective gas atmosphere, carrying out asymmetric boron protonation reaction on the allene phosphine oxide compound shown in the structure of the formula II, pinacol borate, copper (I) catalyst, chiral ligand, organic alkaline compound, proton additive in a polar organic solvent to obtain the α-carbon chiral phosphine compound; the chiral ligand is a cyclic phosphine ligand (S, S)-Ph-BPE or a cyclic phosphine ligand (R, R)-Ph-BPE;

[0042]

[0043] In the present application, all the preparation raw materials / components are commercially available products well known to those skilled in the art without special instructions.

[0044] The present application does not have special requirements for the source of the allene phosphine oxide compound shown in the structure of the formula II, which can be prepared by using the preparation method well known to those skilled in the art.

[0045] In the present application, the structural formula of the cyclic phosphine ligand (S, S)-Ph-BPE is shown in the formula III:

[0046]

[0047] In the present application, the structural formula of the cyclic phosphine ligand (R, R)-Ph-BPE is shown in the formula IV:

[0048]

[0049] In the present application, the copper (I) catalyst is preferably one or more of CuCl, CuBr, CuI, CuOAc, CuTc and Cu(CH3CN)4PF6, and more preferably CuOAc.

[0050] In the present application, the organic basic compound is sodium tert-butoxide.

[0051] In the present application, the proton additive is methanol.

[0052] In the present application, when the organic basic compound is sodium tert-butoxide and the proton additive is methanol, the chiral ligand and the copper (I) catalyst generate in situ alkoxycopper (I) complex under the action of the organic basic compound, wherein the alkoxycopper (I) complex is tert-butoxycopper generated by the copper catalyst and the base sodium tert-butoxide at the start of the catalytic reaction, or methoxycopper generated by the reaction with methanol after protonation in the catalytic cycle.

[0053] In the present application, the polar organic solvent is preferably at least one selected from tetrahydrofuran, methyl tert-butyl ether, diethyl ether and toluene, and more preferably toluene.

[0054] In the present application, the molar ratio of the bisalkenyl phosphine oxide compound of the structure shown in formula II to the pinacol borate is preferably 1:(1-2), more preferably 1:(1-1.7), and most preferably 1:(1-1.5).

[0055] In the present application, the molar ratio of the bisalkenyl phosphine oxide compound of the structure shown in formula II to the copper (I) catalyst is preferably 1:0.05.

[0056] In the present application, the molar ratio of the bisalkenyl phosphine oxide compound of the structure shown in formula II to the chiral ligand is preferably 1:0.06.

[0057] In the present application, the molar ratio of the bisalkenyl phosphine oxide compound of the structure shown in formula II to the proton additive is preferably 1:2.

[0058] In the present application, the molar ratio of the bisalkenyl phosphine oxide compound of the structure shown in formula II to the organic basic compound is preferably 1:0.2.

[0059] The present application does not have special requirements for the amount of the polar organic solvent, which only needs to ensure that the asymmetric boron protonation reaction proceeds smoothly.

[0060] In the present application, the temperature of the asymmetric boron protonation reaction is -30 to -60℃, and more preferably -55℃. In the present application, the holding time of the asymmetric boron protonation reaction is preferably 12 to 24 hours. In the present application, the asymmetric boron protonation reaction is preferably carried out under stirring.

[0061] In the present application, the protective gas is preferably nitrogen.

[0062] In the present application, the mixing order of the raw materials of the asymmetric boron protonation reaction is as follows: after the copper (I) catalyst, the chiral ligand, the organic basic compound and the polar organic are mixed under stirring at room temperature for 30 minutes in the atmosphere of the protective gas, the temperature is lowered to the temperature of the asymmetric boron protonation reaction, and pinacol borate, the allene-based phosphine oxide compound represented by the structure of formula II and the proton additive are sequentially added.

[0063] In the present application, the reaction liquid is obtained after the asymmetric boron protonation reaction, and the reaction liquid is preferably subjected to post-treatment to obtain the α-carbon chiral phosphine compound. In the present application, the post-treatment preferably comprises the following steps: the reaction liquid is concentrated to obtain a concentrate; and the concentrate is subjected to column chromatography purification to obtain the α-carbon chiral phosphine compound. In the present application, the eluent used in the column chromatography purification is preferably a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is preferably 1:1.

[0064] In order to further illustrate the present application, the technical solutions provided by the present application are described in detail below in combination with the drawings and examples, but they should not be understood as limiting the scope of protection of the present application.

[0065] In the examples of the present application, the reagents and solvents used are commercially available analytical pure. The reaction solvent is distilled under standard conditions to obtain anhydrous and oxygen-free solvent, and the MTBE, THF and toluene used in the reaction are dried by sodium reflux. Petroleum ether (60-90℃) and ethyl acetate are used as eluents for product purification, and 200-300 mesh silica gel is used for separation and purification. NMR testing is performed on a JEOL 400 and JEOL 600 nuclear magnetic resonance spectrometer, with CDCl3 as the solvent and CDCl3 (δ(1H): 7.26 ppm; δ(13C): 77.16 ppm) as the chemical shift reference. The enantioselectivity is analyzed by liquid chromatography.

[0066] The preparation method of the allene-based phosphine oxide compound comprises the following steps:

[0067] (1) Preparation of alkyne alcohol:

[0068] Method A:

[0069]

[0070] According to the reaction scheme shown in Formula 1 : a Schlenk flask was charged with a magnetic stir bar, evacuated and replaced with nitrogen, repeated three times, benzaldehyde (1 equiv) and tetrahydrofuran (0.1 M) were added sequentially, n-BuLi (2.5 M in hexane, 1 equiv) was added dropwise over 30 min at 0 °C, after the addition was complete, the reaction was stirred at 0 °C for one hour, then paraformaldehyde (1.4 equiv) was added, the reaction was allowed to warm to room temperature and stirred overnight. After the reaction was complete, the reaction was quenched by the slow addition of saturated ammonium chloride, allowed to settle and separate, the organic phase was removed using a separatory funnel and the aqueous phase was extracted three times with ethyl acetate, the organic phases were combined and the organic phase was washed with saturated sodium chloride solution, finally the organic phase was dried over anhydrous sodium sulfate. The crude product was isolated by filtration and concentrated, the crude product was separated by column chromatography (petroleum ether: ethyl acetate = 2: 1, v:v) to give 3-phenyl-2-propyn-1-ol in 86% yield.

[0071] Method B:

[0072]

[0073] According to the reaction scheme shown in Formula 2: a Schlenk flask was charged with a magnetic stir bar, evacuated and replaced with nitrogen, repeated three times, Pd(PPh3)2Cl2(1 mol%) and Cul (2 mol%) were added under nitrogen, then Et3N (0.25 M), aryl iodide (1 equiv) and propargyl alcohol (1.1 equiv) were added sequentially, the reaction was heated to 60 °C and stirred for a further 5 hours. After the reaction was complete, the reaction was cooled to room temperature, the reaction was filtered, the solid residue was washed with Et3N, the washings and organic phase were combined, the solvent was removed using a rotary evaporator, the crude product was separated by column chromatography (petroleum ether: ethyl acetate = 2: 1, v:v) to give the product. The propargyl alcohols shown in Table 1 were obtained according to Method B.

[0074] Propargyl alcohols obtained according to Method B

[0075]

[0076] (2) Preparation of chlorophosphine:

[0077]

[0078] According to the reaction scheme shown in Formula 3: a 250 mL three-necked flask equipped with a reflux condenser and a magnetic stir bar was evacuated and replaced with nitrogen three times, and then magnesium (Mg) chips (1.2 equiv) and a small amount of tetrahydrofuran were sequentially added, followed by a small amount of elemental iodine and the mixture was heated with a heat gun until the color disappeared. A tetrahydrofuran (1.0 M) solution of R-Br (1 equiv) was added dropwise, and the reflux was maintained throughout the addition process. After the addition was completed, the reaction was heated with an oil bath at 60°C for 4 hours, and then cooled to room temperature.

[0079]

[0080] According to the reaction scheme shown in Formula 4: under nitrogen protection, Et2NPCl2 (1 equiv) and tetrahydrofuran (0.67 M) were added, and the temperature was lowered to 0°C, and the Grignard reagent (RMgBr, 2.05 equiv) was added dropwise, and the reaction was stirred at 0°C for 3 hours, and then the solvent was removed on a rotary evaporator, leaving a brown slurry. Cyclohexane was added to the slurry, and filtered through a sand core funnel, and then anhydrous HC1 gas was bubbled into the solution for 1 hour under constant stirring, and the resulting reaction liquid was filtered under nitrogen protection, and the solvent was removed on a rotary evaporator, and immediately used in the next reaction. The phosphine chlorides shown in Table 2 were prepared according to the above method.

[0081] Table 2 Phosphine chlorides prepared according to the scheme shown in Formula 4

[0082]

[0083] (3) Preparation of allenes:

[0084]

[0085] According to the reaction scheme shown in Formula 5: a magnetic stir bar was added to a Schlenk flask, evacuated and replaced with nitrogen three times, and then the alkyne alcohol (1 equiv), triethylamine (1.5 equiv) and tetrahydrofuran (0.33 M) were added, and then cooled to -78°C, and R 1 A tetrahydrofuran solution of 2PCl (1.2 equiv) was slowly added to the reaction bottle, and after the addition was completed, the reaction was raised to room temperature (3i and 3j were heated to 60°C for further reaction), and after the reaction was completed, dilute HC1 (0.1 M) was slowly added to quench the reaction, and the layers were allowed to separate, and the organic phase was removed with a separatory funnel, and the aqueous phase was extracted with ethyl acetate three times, and the organic phases were combined, and then washed with saturated sodium chloride solution, and finally dried with anhydrous sodium sulfate. After filtration and concentration, the crude product was separated by column chromatography (petroleum ether: ethyl acetate = 1:1, v:v) to obtain the allene phosphine oxide compounds shown in Table 3.

[0086] Table 3 Allene phosphine oxide compounds used in the examples of the present application

[0087]

[0088] Example 1

[0089]

[0090] According to the reaction scheme shown in formula 6: take 25 mL Schlenk tube, under the protection of nitrogen, add cuprous acetate (5 mol% of the vinylogous phosphine oxide compound), (S, S)-Ph-BPE (6 mol% of the vinylogous phosphine oxide compound), sodium tert-butoxide (20 mol% of the vinylogous phosphine oxide compound) and toluene (2 mL) in turn, stir for 30 minutes at room temperature, cool to-55℃, add B2pin2 (1.2 equiv), then add the vinylogous phosphine oxide compound (0.2 mmol, 1.0 equiv) and methanol (2 equiv). After the reaction is completed, the reaction solution is quenched directly by using ammonium chloride solution and concentrated, and the crude product is separated by column chromatography (petroleum ether: ethyl acetate = 1:1, v:v) to obtain the target product, i.e. the α-carbon chiral phosphine compound with the structure shown in formula I; wherein the vinylogous phosphine oxide compound is the vinylogous phosphine oxide compound recorded as 1a, 1b, 1c, 1d, 1e, 1f, 1g, 1h, 1i, 1j, 1k, 1l, 1m, 1n, 1o, 1p, 1q, 1r, 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h, 3i, 3j or 3k in Table 3 prepared by the above method;

[0091] The α-carbon chiral phosphine compound prepared in this example is specifically the α-carbon chiral phosphine compound recorded as 2a, 2b, 2c, 2d, 2e, 2f, 2g, 2h, 2i, 2j, 2k, 2l, 2m, 2n, 2o, 2p, 2q, 2r, 4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i, 4j or 4k in Table 4 and Table 5;

[0092] Specific structure, yield and ee value of part of the α-carbon chiral phosphine compound in Table 4 a

[0093]

[0094] Specific structure, yield and ee value of the remaining α-carbon chiral phosphine compound in Table 5 a

[0095]

[0096] From Table 4 and Table 5, it can be concluded that:

[0097] When the substituent is a halogen (F, CI and Br), the reactant undergoes asymmetric boron protonation smoothly to give 2b-d in excellent yield and high ee value. Reactants with electron-donating groups also give the corresponding products 2e-g in excellent yield and ee value of more than 96%, while electron-withdrawing groups reduce the enantioselectivity (2h-j). When the α-phenyl group has a meta-substituent, the allene-based diphenylphosphine oxide reactants are successfully converted into the corresponding products 2k and 2l in 99%, 81% yield and 95%, 93% ee value, respectively. When the α-phenyl group has an ortho-substituent, steric hindrance is observed, and the products 2m and 2n are obtained in moderate yield with 76% and 89% ee value, respectively, while the naphthyl-substituted substrate gives the product 2o in 60% yield and 44% ee value. The thienyl-substituted allene-based diphenylphosphine oxides give the corresponding products 2p and 2q in 95%, 85% yield and 94%, 81% ee value, respectively. Boron protonation of the α-methyl-allene-based diphenylphosphine oxide gives the corresponding product 2r in 68% yield and 79% ee value. When the phosphorus atom has an aromatic substituent with a para-, meta- or ortho-substituent, the asymmetric boron protonation reaction proceeds smoothly to give the products 4a-f in 50-83% yield and 78-96% enantioselectivity. Under the same conditions, the dicyclohexyl- or diisobutyl-substituted allene-based phosphine oxides give the target products (4g-h) in moderate yield and good enantiomeric excess (80-86% ee). The allene-based phosphonates are also suitable for the reaction, and the products 4i and 4j are obtained in 45% and 88% yield with 94% and 95% ee value, respectively. The product 4k is obtained from the allene-based phosphorodiamide in moderate yield and ee value.

[0098] Example 2

[0099] A 100 mL Schlenk tube was charged with cuprous acetate (19.6 mg, 5 mol%), (S,S)-Ph-BPE (97.3 mg, 6 mol%), sodium tert-butoxide (20 mol%) and toluene (30 mL) under nitrogen protection, stirred at room temperature for 30 minutes, cooled to -55 °C, and then added B2pin2(0.98 g, 3.84 mmol), followed by 1a (1.0 g, 3.2 mmol) and methanol (2 equiv). After the reaction was completed, the reaction solution was directly concentrated, and the crude product was separated by column chromatography (petroleum ether: ethyl acetate = 1:1, v:v) to obtain the target product 2a.

[0100] This example investigates the asymmetric boron protonation of 1a on a gram scale, and 2a is obtained in 96% yield and 96% ee value, which demonstrates the effectiveness of the preparation method provided by the present application.

[0101] Example 3

[0102] This example screened the types of chiral ligands:

[0103] This example screened the types of chiral ligands according to the reaction scheme shown in Formula 7, using the reaction of substrate la and B2pin2 as a model. The ligands used in the reaction were screened at room temperature using Cu(CH3CN)4PF6 as a catalyst, tetrahydrofuran as a solvent, sodium tert-butoxide as a base, and methanol as a proton additive. The specific parameters of the experiment are shown in Table 6.

[0104]

[0105] Table 6: Types of chiral ligands and specific reaction conditions used in Example 3

[0106]

[0107] Note 1: la (0.2 mmol), B2pin2 (0.24 mmol), Cu(CH3CN)4PF6 (5 mol% of la), L1-8 (6 mol% of la), L9-10 (12 mol% of la), NaO t Bu (20 mol% of la), MeOH (0.4 mmol), THF (2 mL).

[0108] Note 2: Yield after separation and purification.

[0109] L1-L10 in Table 6 are as follows:

[0110]

[0111] The results in Table 6 show that when (S)-BINAP is used as the ligand, both the yield and enantioselectivity of the reaction are low, 20% and 13% ee, respectively (Table 6, entry 1). Then, ligand L2 with BINAP skeleton is tried in this example, although the yield is increased, the ee value is still very low (Table 6, entry 2). When the ligand L3 with large steric hindrance is used, the yield is 49% (Table 6, entry 3). When the ligand L4 is used, the product is obtained in 72% yield and 13% ee (Table 6, entry 4). The cyclic phosphine ligand (S,S)-Ph-BPE (L5) promotes the reaction, and the yield and enantioselectivity are significantly improved, and the ee value of the product is 63% (Table 6, entry 5). When the ligand L6 with the same skeleton is used instead of L5, the reaction has almost no enantioselectivity (Table 6, entry 6). When L7 is used as the ligand, no reaction occurs (Table 6, entry 7), and when L8 is used as the ligand, the ee value of the product is 35% (Table 6, entry 8). Further screening shows that when other ligands such as (R)-MeO-MOP and phosphinamide ligands are used, the product is obtained in similar yield, but without enantioselectivity (Table 6, entries 9 and 10). From the results in Table 6, it can be seen that the ligand L5 is the best ligand.

[0112] Example 4

[0113] In this example, the types of copper (I) catalysts are screened:

[0114] Example 3 determines the best chiral ligand. In order to further improve the enantioselectivity of the reaction, in this example, according to the reaction scheme shown in formula 8 and the reaction conditions in Table 7, the reaction temperature is reduced to -30°C, and the effect of copper (I) catalyst on the reaction is studied, and the results are shown in Table 7.

[0115] From the results of Table 7, it can be seen that the yield and enantioselectivity are significantly improved when the reaction temperature is lowered from room temperature to -30 °C. The first study in this example is the effect of the copper salt on the catalysis of the reaction. When Cu(CH3CN)4PF6is used as the catalyst, both the yield and the ee value are improved, which are 77% and 85% respectively (Table 7, entry 1). When CuCl is used as the catalyst, the product is obtained with a similar ee value (Table 7, entry 2). When CuBr and Cul are used as the catalyst, the yield can also reach about 80%, but the ee value is relatively low, which are only 48% and 37% respectively (Table 7, entries 3 and 4). When CuOAc is used as the catalyst, the product is obtained with a yield of 88% and an ee value of 90% (Table 7, entry 5). When CuTc is used as the catalyst, the yield is 80% and the ee value is 87% (Table 9, entry 6). When CuCl2is used as the catalyst, the yield is significantly reduced, but the ee value is still maintained above 80% (Table 7, entry 7). When CuBr2is used as the catalyst, the ee value is only 33% (Table 7, entry 8). When Cu(OAc)2and Cu(CF3SO3)2are used as the catalyst, similar yields and poor enantioselectivity are obtained (Table 7, entries 9 and 10). Therefore, CuOAc is the best catalyst.

[0116]

[0117] Table 7 Screening of copper (I) catalysts 1

[0118]

[0119] Note 1: la (0.2 mmol), B2pin2(0.24 mmol), Cu catalyst (5 mol%), (S,S)-Ph-BPE (6 mol%), NaO t Bu (20 mol%), MeOH (0.4 mmol), THF (2 mL).

[0120] Note 2: Yield after separation and purification.

[0121] Example 5

[0122] This example studies the screening of the reaction conditions;

[0123] The reaction is carried out according to the reaction scheme of formula 9 and the reaction conditions of Table 10, and the results are shown in Table 8.

[0124] From the results of Table 10, it can be seen that when the temperature is lowered to -40 °C, the enantioselectivity of the product does not show a significant change (Table 8, entries 1 and 2). When KO t Bu is used instead of NaO tNo reaction occurred when Bu was used as the base (Table 8, entry 3); when LiO t When Bu was used as the base, the ee value was only 43% (Table 8, entry 4). When NaO t When Bu was used as the base, the temperature was further lowered to -50°C, and the yield and ee value of the product were significantly reduced (Table 8, entry 5). During the reaction, insoluble solids were observed, which were presumably due to the low solubility of the reactants and product. To further improve the enantioselectivity, different solvents, toluene, diethyl ether and methyl tert-butyl ether, were then investigated. When toluene was used as the solvent, the yield of the product was 93% and the ee value was 93% (Table 8, entry 6), while when diethyl ether and methyl tert-butyl ether were used as the solvents, the yields were only 60% and 40%, respectively (Table 8, entries 7 and 8). When toluene was used as the solvent, the temperature was further lowered, and at -55°C, the target product was obtained in a yield of 99% and an ee value of 98% (Table 8, entry 9). When the temperature was lowered to -60°C, the yield was 92% (Table 8, entry 10). Thus, the optimal reaction conditions were determined by the present application: 5 mol% CuOAc as the catalyst, 6 mol% (S,S)-Ph-BPE as the ligand, 20 mol% NaOt-Bu as the base, toluene as the solvent, and the reaction was carried out at -55°C.

[0125]

[0126] Optimization of reaction conditions 1

[0127]

[0128]

[0129] Note 1: 1a (0.2 mmol), B2pin2 (0.24 mmol), CuOAc (5 mol%), (S,S)-Ph-BPE (6 mol%), base (20 mol%), MeOH (0.4 mmol), solvent (2 mL).

[0130] Note 2: Yield after separation and purification.

[0131] The structural characterization data of the homoallylic phosphine oxide compound of the structure shown in Formula II and the α-carbon chiral phosphine compound of the structure shown in Formula I prepared in the examples of the present application are as follows:

[0132]

[0133] diphenyl(1-(4-(trifluoromethoxy)phenyl)propa-1,2-dien-1-yl)phosphine oxide (1g): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1 : 1) as eluent, 1.17 g, 74% yield, white solid, m.p. 90-91 °C. 1 H NMR (400 MHz, CDC13) δ 7.77-7.72 (m, 4H), 7.64 (d, J = 8.8 Hz, 2H), 7.54-7.50 (m, 2H), 7.48-7.42 (m, 4H), 7.10 (d, J = 8.4 Hz, 2H), 4.92 (d, J = 10.8 Hz, 2H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 213.5 (d, J = 6.6 Hz), 148.6, 132.2 (d, J = 2.3 Hz), 131.85 (d, J = 9.7 Hz), 131.8 (d, J = 105.7 Hz), 130.7 (d, J = 5.9 Hz), 129.8 (d, J = 4.5 Hz), 128.5 (d, J = 12.6 Hz), 121.1, 120.8, 99.8 (d, J = 10.0 Hz), 79.0 (d, J = 12.2 Hz). 31 P NMR (162 MHz, CDC13) δ 29.3. 19 F NMR (376 MHz, CDC13) δ -57.8. HRMS (ESI-MS) m / z calcd. for C 22 H 17 F3O2P [M + H] + : 401.0913, found: 401.0918.

[0134]

[0135] methyl 4-(1-(diphenylphosphoryl)propa-1,2-dien-1-yl)benzoate (1h): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1 : 1) as eluent, 0.86 g, 84% yield, white solid, m.p. 156-157 °C. 1 H NMR (400 MHz, CDC13) δ 7.91 (d, J = 8.4 Hz, 2H), 7.77-7.68 (m, 6H), 7.51 (dt, J = 7.6, 1.2 Hz, 2H), 7.45-7.41 (m, 4H), 4.95 (d, J = 10.4 Hz, 2H), 3.86 (s, 3H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 214.0 (d, J = 6.3 Hz), 166.8, 136.9 (d, J = 5.4 Hz), 132.1 (d, J = 2.2 Hz), 131.8 (d, J = 9.6 Hz), 131.76 (d, J = 100 Hz), 129.9, 129.1, 128.5 (d, J = 12.6 Hz), 128.2 (d, J = 4.6 Hz), 100.6 (d, J = 100.5 Hz), 79.2 (d, J = 12.2 Hz), 52.2. 31 P NMR (162 MHz, CDC13) δ 29.2. HRMS (ESI-MS) m / z calcd for C 23 H 19 O3PK[M+K] + :413.0703, found:413.0702.

[0136]

[0137] diphenyl(1-(4-(trifluoromethyl)phenyl)propa-1,2-dien-1-yl)phosphine oxide (1i): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1 : 1) as eluent, 0.77 g, 39% yield, white solid, m.p. 89-90 °C. 1H NMR (400 MHz, CDCI3) δ 7.77-7.72 (m, 6H), 7.55-7.39 (m, 8H), 4.96 (d, J = 10.8 Hz, 2H). 13 C{ 1 H} NMR (101 MHz, CDCI3) δ 213.9 (d, J = 6.2 Hz), 135.9 (d, J = 2.9 Hz), 132.3, 132.1, 131.8 (d, J = 9.6 Hz), 131.6 (d, J = 99.9 Hz), 129.6 (q, J = 32.7 Hz), 128.55, 128.54 (d, J = 12.2 Hz), 125.6 (d, J = 3.6 Hz), 124.1 (q, J = 273.2 Hz), 100.2 (d, J = 99.8 Hz), 79.3 (d, J = 11.9 Hz). 31 P NMR (162 MHz, CDCI3) δ 29.1. 19 F NMR (376 MHz, CDCI3) δ -62.7. HRMS (ESI-MS) m / z calcd. for C 22 H 17 F3OP[M+H] + : 385.0964, found: 385.0964.

[0138]

[0139] 4-(1-(diphenylphosphoryl)propa-1,2-dien-1-yl)benzonitrile (1j): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 1.47 g, 91% yield, white solid, m.p. 150-151 °C. 1 H NMR (400 MHz, CDCI3) δ 7.76-7.71 (m, 6H), 7.56-7.54 (m, 4H), 7.45 (dt, J = 7.6, 2.8 Hz, 4H), 4.99 (d, J = 10.8 Hz, 2H). 13 C{ 1H NMR (101 MHz, CDC13) δ 214.0 (d, J = 6.3 Hz), 137.3 (d, J = 5.6 Hz), 132.40, 132.36 (d, J = 2.6 Hz), 131.8 (d, J = 9.6 Hz), 131.5 (d, J = 108.3 Hz), 128.8 (d, J = 4.5 Hz), 128.6 (d, J = 12.6 Hz), 118.8, 111.2, 100.3 (d, J = 100.2 Hz), 79.5 (d, J = 11.8 Hz). 31 P NMR (162 MHz, CDC13) δ 29.0. HRMS (ESI-MS) m / z calcd for C 22 H 17 NOP [M+H] + : 342.1042, found: 342.1032.

[0140]

[0141] (1-(3-chloro-4-fluorophenyl)propa-1,2-dien-1-yl)diphenylphosphine oxide (1k): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 1.47 g, 86% yield, white solid, m.p. 133-134 °C. 1 H NMR (400 MHz, CDC13) δ 7.76-7.71 (m, 4H), 7.63 (dd, J = 6.8, 2.0 Hz, 1H), 7.58-7.50 (m, 3H), 7.47-7.42 (m, 4H), 7.01 (t, J = 8.8 Hz, 1H), 4.93 (d, J = 10.8 Hz, 2H). 13 C{ 1H}NMR (101 MHz, CDCI3) δ 213.3 (d, J = 6.9 Hz), 157.5 (d, J = 251.3 Hz), 132.2 (d, J = 2.1 Hz), 131.8 (d, J = 9.7 Hz), 131.5 (d, J = 107.8 Hz), 130.3 (d, J = 5.2 Hz), 129.3, 129.24, 129.2, 128.5 (d, J = 12.6 Hz), 128.1 (dd, J = 6.8, 4.7 Hz), 121.2 (d, J = 18.2 Hz), 116.7 (d, J = 21.4 Hz), 99.2 (d, J = 100.7 Hz), 79.3 (d, J = 12.2 Hz). 31 P NMR (162 MHz, CDCI3) δ 29.1. 19 F NMR (376 MHz, CDCI3) δ -116.4. HRMS (ESI-MS) m / z calcd for C 21 H 16 ClFOP[M + H] + : 369.0606, found: 369.0616.

[0142]

[0143] (1-(3-methoxyphenyl)propa-1,2-dien-1-yl)diphenylphosphine oxide (1 1 ): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1 :1 ) as eluent, 1.41 g, 69% yield, viscous oil. 1 H NMR (400 MHz, CDCI3) δ 7.79-7.78 (m, 1 H), 7.77-7.75 (m, 2H), 7.74-7.73 (m, 1 H), 7.52-7.47 (m, 2H), 7.45-7.40 (m, 4H), 7.21 -7.13 (m, 3H), 6.76-6.73 (m, 1 H), 4.89 (d, J = 10.8 Hz, 2H), 3.70 (s, 3H). 13 C{ 1H NMR (101 MHz, CDC13) δ 213.6 (d, J = 6.9 Hz), 159.7, 133.3 (d, J = 5.5 Hz), 132.2 (d, J = 107.7 Hz), 132.0 (d, J = 2.9 Hz), 131.9 (d, J = 9.6 Hz), 129.7, 128.4 (d, J = 12.6 Hz), 120.9 (d, J = 5.0 Hz), 113.8, 113.5 (d, J = 5.1 Hz), 100.8 (d, J = 101.0 Hz), 78.6 (d, J = 12.5 Hz), 55.3. 31 P NMR (162 MHz, CDC13) δ 28.9. HRMS (ESI-MS) m / z calcd for C 22 H 20 O2P[M+H] + : 347.1195, found: 347.1183.

[0144]

[0145] (1-(2-chlorophenyl)propa-1,2-dien-1-yl)diphenylphosphine oxide (1m): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 0.64 g, 37% yield, white solid, m.p. 107-108 °C. 1 H NMR (400 MHz, CDC13) δ 7.83-7.78 (m, 4H), 7.77-7.75 (m, 1H), 7.51-7.47 (m, 2H), 7.44-7.40 (m, 4H), 7.34-7.32 (m, 1H), 7.18-7.12 (m, 2H), 4.86 (d, J = 10.8 Hz, 2H). 13 C{ 1H NMR (101 MHz, CDC13) δ 213.7 (d, J = 6.3 Hz), 133.9 (d, J = 5.9 Hz), 132.0 (d, J = 2.4 Hz), 131.8 (d, J = 9.6 Hz), 131.6 (d, J = 107.2 Hz), 131.1 (d, J = 1.9 Hz), 130.7 (d, J = 5.9 Hz), 130.1, 129.2, 128.3 (d, J = 12.5 Hz), 127.0, 97.5 (d, J = 101.7 Hz), 77.9 (d, J = 12.1 Hz). 31 P NMR (162 MHz, CDC13) δ 28.8. HRMS (ESI-MS) m / z calcd for C 21 H 17 ClOP[M+H] + : 351.0700, found: 351.0704.

[0146]

[0147] (1-(2-iodophenyl)propa-1,2-dien-1-yl)diphenylphosphine oxide (1n): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 1.21 g, 87% yield, white solid, m.p. 106-107 °C. 1 H NMR (400 MHz, CDC13) δ 7.86-7.79 (m, 5H), 7.69 (dt, J = 8.0, 1.2 Hz, 1H), 7.52-7.47 (m, 2H), 7.45-7.40 (m, 4H), 7.24-7.22 (m, 1H), 6.89 (dt, J = 7.6, 1.2 Hz, 1H), 4.96 (d, J = 10.4 Hz, 2H). 13 C{ 1 H NMR (101 MHz, CDC13) δ 213.1 (d, J = 6.7 Hz), 140.0, 135.7 (d, J = 5.9 Hz), 132.02 (d, J = 9.2 Hz), 132.01, 131.4 (d, J = 99.5 Hz), 130.2, 129.5, 128.4, 128.3 (d, J = 12.5 Hz), 103.7 (d, J = 100.9 Hz), 100.7 (d, J = 5.6 Hz), 79.3 (d, J = 12.0 Hz).31 P NMR (162 MHz, CDC13) δ 27.9. HRMS (ESI-MS) m / z calcd for C 21 H 17 IOP [M+H] + : 443.0056, found: 443.0061.

[0148]

[0149] (1-(naphthalen-1-yl)propa-1,2-dien-1-yl)diphenylphosphine oxide (10): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 0.63 g, 54% yield, white solid, m.p. 141-142 °C. 1 H NMR (400 MHz, CDC13) δ 8.14 (d, J = 8.0 Hz, 1H), 7.82-7.77 (m, 5H), 7.72 (d, J = 8.0 Hz, 1H), 7.67 (d, J = 7.2 Hz, 1H), 7.51-7.43 (m, 4H), 7.40-7.33 (m, 5H), 4.91 (d, J = 10.8 Hz, 2H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 213.6 (d, J = 6.7 Hz), 134.1, 132.0, 131.9 (d, J = 9.5 Hz), 131.8 (d, J = 4.6 Hz), 131.78 (d, J = 106.6 Hz), 129.2 (d, J = 4.9 Hz), 128.6 (d, J = 9.1 Hz), 128.3 (d, J = 12.5 Hz), 127.6 (d, J = 3.7 Hz), 126.3, 125.9, 125.4, 125.1, 98.3 (d, J = 98.7 Hz), 76.9 (d, J = 15.7 Hz). 31 P NMR (162 MHz, CDC13) δ 28.0. HRMS (ESI-MS) m / z calcd for C 25 H 20 OP [M+H] + : 367.1246, found: 367.1250.

[0150]

[0151] diphenyl(1-(thiophen-3-yl)propa-1,2-dien-1-yl)phosphine oxide(1p): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1 : 1) as eluent, 0.57 g, 66% yield, reddish solid, m.p. 133-134 °C. 1 H NMR (400 MHz, CDC13) δ 7.78-7.73 (m, 4H), 7.54-7.50 (m, 3H), 7.46-7.42 (m, 4H), 7.23-7.21 (m, 1H), 7.16 (d, J = 5.2 Hz, 1H), 4.89 (d, J = 11.2 Hz, 2H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 213.0 (d, J = 6.6 Hz), 132.1 (d, J = 2.4 Hz), 131.9 (d, J = 9.6 Hz), 131.8 (d, J = 107.6 Hz), 131.2 (d, J = 5.7 Hz), 128.4 (d, J = 12.5 Hz), 127.3 (d, J = 5.9 Hz), 125.5, 123.8 (d, J = 2.9 Hz), 96.6 (d, J = 102.2 Hz), 78.7 (d, J = 12.5 Hz). 31 P NMR (162 MHz, CDC13) δ 29.3. HRMS (ESI-MS) m / z calcd for C 19 H 16 OPS[M+H] + :323.0654, found:323.0650.

[0152]

[0153] diphenyl(1-(thiophen-2-yl)propa-1,2-dien-1-yl)phosphine oxide(1q): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1 : 1) as eluent, 1.32 g, 83% yield, yellow solid, m.p. 111-112 °C.1 H NMR (400 MHz, CDC13) δ 7.80-7.79 (m, 1H), 7.78-7.76 (m, 2H), 7.75-7.74 (m, 1H), 7.55-7.50 (m, 2H), 7.47-7.42 (m, 4H), 7.28-7.27 (m, 1H), 7.18 (d, J = 5.2 Hz, 1H), 6.89-6.87 (m, 1H), 4.95 (d, J = 10.8 Hz, 2H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 212.3 (d, J = 5.9 Hz), 134.1 (d, J = 8.7 Hz), 132.2 (d, J = 2.4 Hz), 131.9 (d, J = 9.7 Hz), 131.6 (d, J = 108.2 Hz), 128.4 (d, J = 12.7 Hz), 127.9, 127.6 (d, J = 2.6 Hz), 125.7, 96.5 (d, J = 100.7 Hz), 79.5 (d, J = 11.9 Hz). 31 P NMR (162 MHz, CDC13) δ 28.7. HRMS (ESI-MS) m / z calcd for C 19 H 16 OPS [M+H] + : 323.0654, found: 323.0662.

[0154]

[0155] bis(4-fluorophenyl)(1-phenylpropa-1,2-dien-1-yl)phosphine oxide (3a): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 0.53 g, 31% yield, yellow solid, m.p. 98-99 °C. 1 H NMR (400 MHz, CDC13) δ 7.86-7.74 (m, 2H), 7.57 (d, J = 6.8 Hz, 4H), 7.30-7.11 (m, 7H), 4.92 (d, J = 10.8 Hz, 2H). 13 C{ 1H}NMR (101 MHz, CDC13) δ 213.6 (d, J = 7.0 Hz), 165.2 (dd, J = 254.4, 3.0 Hz), 134.4, 134.3, 134.2, 131.7 (dd, J = 29.2, 5.5 Hz), 128.9, 128.7 (d, J = 65.1 Hz), 128.3 (d, J = 4.9 Hz), 128.0 (dd, J = 111.4, 3.0 Hz), 115.9 (dd, J = 21.6, 13.9 Hz), 100.9 (d, J = 102.7 Hz), 78.9 (d, J = 12.6 Hz). 31 P NMR (162 MHz, CDC13) δ 27.7. 19 F NMR (376 MHz, CDC13) δ -106.3. HRMS (ESI-MS) m / z calcd for C 21 H 16 F2OP[M+H] + :353.0901, found:353.0892.

[0156]

[0157] bis(3,5-dimethylphenyl)(1-phenylpropa-1,2-dien-1-yl)phosphine oxide (3b): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 0.86 g, 46% yield, white solid, m.p. 125-126 °C. 1 H NMR (400 MHz, CDC13) δ 7.57 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 12.4 Hz, 4H), 7.26-7.22 (m, 2H), 7.16 (t, J = 7.2 Hz, 1H), 7.10 (s, 2H), 4.89 (d, J = 10.8 Hz, 2H), 2.30 (s, 12H). 13 C{ 1H NMR (101 MHz, CDC13) δ 213.6 (d, J = 6.8 Hz), 137.9 (d, J = 13.2 Hz), 133.7 (d, J = 2.6 Hz), 132.2 (d, J = 5.2 Hz), 131.9 (d, J = 106.5 Hz), 129.4 (d, J = 9.7 Hz), 128.6, 128.4 (d, J = 4.6 Hz), 127.5, 100.8 (d, J = 99.8 Hz), 78.3 (d, J = 12.3 Hz), 21.4. 31 P NMR (162 MHz, CDC13) δ 30.4. HRMS (ESI-MS) m / z calcd for C 25 H 25 OPNa[M + Na] + : 395.1535, found: 395.1530.

[0158]

[0159] (1-(4-bromophenyl)propa-1,2-dien-1-yl)bis(3,5-dimethylphenyl)phosphine oxide (3c): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 1.28 g, 61% yield, white solid, m.p. 67-68 °C. 1 H NMR (400 MHz, CDC13) δ 7.47 (d, J = 8.4 Hz, 2H), 7.36-7.31 (m, 4H), 7.11 (s, 2H), 4.89 (d, J = 10.8 Hz, 2H), 2.30 (s, 12H). 13 C{ 1 H NMR (101 MHz, CDC13) δ 213.4 (d, J = 6.7 Hz), 138.1 (d, J = 13.2 Hz), 133.8 (d, J = 2.5 Hz), 131.7, 131.6 (d, J = 106.6 Hz), 131.4 (d, J = 5.2 Hz), 130.0 (d, J = 4.6 Hz), 129.4 (d, J = 9.6 Hz), 121.7, 100.2 (d, J = 99.5 Hz), 78.8 (d, J = 12.0 Hz), 21.4. 31P NMR (162 MHz, CDC13) δ 30.4. HRMS (ESI-MS) m / z calcd for C 25 H 24 BrOPNa[M+Na] + : 475.0623, found: 475.0618.

[0160]

[0161] bis(3-methoxyphenyl)(1-(p-tolyl)propa-1,2-dien-1-yl)phosphine oxide (3d): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 0.54 g, 46% yield, yellow viscous oil. 1 H NMR (400 MHz, CDC13) δ 7.47 (d, J = 8.0 Hz, 2H), 7.37 (d, J = 1.6 Hz, 1H), 7.34 - 7.29 (m, 3H), 7.26 - 7.22 (m, 2H), 7.07 - 7.00 (m, 4H), 4.88 (d, J = 10.8 Hz, 2H), 3.79 (s, 6H), 2.67 (s, 3H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 213.4 (d, J = 6.7 Hz), 159.5 (d, J = 15.4 Hz), 137.6, 133.5 (d, J = 107.0 Hz), 129.51 (d, J = 14.9 Hz), 129.49, 129.1, 128.9 (d, J = 5.4 Hz), 128.2 (d, J = 4.7 Hz), 124.2 (d, J = 9.8 Hz), 118.3 (d, J = 1.4 Hz), 116.5 (d, J = 10.5 Hz), 100.5 (d, J = 101.3 Hz), 78.5 (d, J = 12.8 Hz), 55.5, 21.3. 31 P NMR (162 MHz, CDC13) δ 30.2. HRMS (ESI-MS) m / z calcd for C 24 H 23 O3PNa[M+Na] + : 413.1277, found: 413.1274.

[0162]

[0163] bis(2-methoxyphenyl)(1-phenylpropa-1,2-dien-1-yl)phosphine oxide(3e): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 0.42 g, 22% yield, white solid, m.p. 118-119 °C. 1 H NMR (400 MHz, CDC13) δ 7.70 (dd, J = 7.6, 1.2 Hz, 1H), 7.66 (dd, J = 7.6, 1.2 Hz, 1H), 7.62 (d, J = 7.6 Hz, 2H), 7.44 (t, J = 7.6 Hz, 2H), 7.22 (t, J = 7.2 Hz, 2H), 7.15 (t, J = 7.2 Hz, 1H), 6.99-6.95 (m, 2H), 6.84 (dd, J = 8.0, 5.2 Hz), 4.87 (d, J = 11.2 Hz, 2H), 3.63 (s, 6H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 213.3 (d, J = 6.7 Hz), 161.4 (d, J = 2.1 Hz), 134.5 (d, J = 8.4 Hz), 133.7, 133.0 (d, J = 5.7 Hz), 128.4, 128.2 (d, J = 4.8 Hz), 127.2, 120.45 (d, J = 110.5 Hz), 120.40 (d, J = 12.6 Hz), 110.9 (d, J = 6.9 Hz), 100.2 (d, J = 107.9 Hz), 77.2 (d, J = 14.3 Hz), 55.6. 31 P NMR (162 MHz, CDC13) δ 27.9. HRMS (ESI-MS) m / z calcd for C 23 H 21 O3PNa[M+Na] + : 399.1121, found: 399.1121.

[0164]

[0165] (1-phenylpropa-1,2-dien-1-yl)di-o-tolylphosphine oxide (3f): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1 : 1) as eluent, 0.34 g, 18% yield, white solid, m.p. 107-108 °C. 1 H NMR (400 MHz, CDC13) δ 7.73 (d, J = 8.0 Hz, 2H), 7.43-7.38 (m, 4H), 7.31-7.20 (m, 5H), 7.16-7.13 (m, 2H), 4.82 (d, J = 10.8 Hz, 2H), 2.58 (s, 6H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 212.7 (d, J = 6.9 Hz), 143.3 (d, J = 7.8 Hz), 132.9 (d, J = 12.5 Hz), 132.3 (d, J = 4.8 Hz), 132.0 (d, J = 2.3 Hz), 131.8 (d, J = 11.0 Hz), 130.5 (d, J = 105.3 Hz), 128.8, 128.5 (d, J = 4.4 Hz), 127.7, 125.4 (d, J = 13.3 Hz), 100.3 (d, J = 99.1 Hz), 77.8 (d, J = 12.5 Hz), 21.8 (d, J = 3.8 Hz). 31 P NMR (162 MHz, CDC13) δ 36.4. HRMS (ESI-MS) m / z calcd. for C 23 H 21 OPNa[M + Na] + : 367.1222, found: 367.1226.

[0166]

[0167] diisobutyl(1-phenylpropa-1,2-dien-1-yl)phosphine oxide (3h): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1 : 1) as eluent, 0.61 g, 74% yield, white oil. 1H NMR (400 MHz, CDCI3) δ 7.61 (d, J = 8.0 Hz, 2H), 7.34-7.30 (m, 2H), 7.26-7.23 (m, 1H), 5.16 (d, J = 10.0 Hz, 2H), 2.19-2.06 (m, 2H), 1.91-1.83 (m, 2H), 1.78-1.70 (m, 2H), 1.03-1.00 (m, 12H). 13 C{ 1 H} NMR (101 MHz, CDCI3) δ 211.3 (d, J = 6.6 Hz), 132.6 (d, J = 4.9 Hz), 128.7, 128.4 (d, J = 3.8 Hz), 127.7, 100.9 (d, J = 86.7 Hz), 77.9 (d, J = 11.1 Hz), 38.7 (d, J = 69.1 Hz), 24.7 (d, J = 8.6 Hz), 23.8 (d, J = 3.7 Hz). 31 P NMR (162 MHz, CDCI3) δ 40.9. HRMS (ESI-MS) m / z calcd for C 17 H 25 OPNa[M+Na] + : 277.1716, found: 277.1715.

[0168]

[0169] dimethyl(1-phenylpropa-1,2-dien-1-yl)phosphonate (3i): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 2: 1) as eluent, 0.70 g, 62% yield, green solid, m.p. 117-118 °C. 1 H NMR (400 MHz, CDCI3) δ 7.52 (d, J = 8.0 Hz, 1H), 7.34-7.30 (m, 2H), 7.26-7.21 (m, 1H), 5.32 (d, J = 3.2 Hz, 2H), 3.76 (d, J = 11.2 Hz). 13 C{ 1H NMR (101 MHz, CDC13) δ 214.0 (d, J = 4.5 Hz), 128.9 (d, J = 22.6 Hz), 128.7, 127.9, 127.6 (d, J = 6.1 Hz), 96.1 (d, J = 190.6 Hz), 78.5 (d, J = 14.7 Hz), 53.3 (d, J = 6.1 Hz). 31 P NMR (162 MHz, CDC13) δ 18.3. HRMS (ESI-MS) m / z calcd for C 11 H 14 O3P[M+H] + : 225.0675, found: 225.0673.

[0170]

[0171] (3k): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 2: 1) as eluent, 0.81 g, 53% yield, brown solid, m.p. 47-48 °C. 1 H NMR (400 MHz, CDC13) δ 7.70 (d, J = 8.0 Hz, 2H), 7.32-7.29 (m, 2H), 7.21 (d, J = 7.2 Hz, 1H), 5.11 (d, J = 11.2 Hz, 2H), 3.12-3.04 (m, 8H), 1.04 (t, J = 7.2 Hz, 12H). 13 C{ 1 H NMR (101 MHz, CDC13) δ 212.6 (d, J = 4.4 Hz), 133.1 (d, J = 6.1 Hz), 128.3, 128.1 (d, J = 4.9 Hz), 127.2, 100.2 (d, J = 150.8 Hz), 76.7 (d, J = 12.9 Hz), 39.5 (d, J = 4.4 Hz), 14.2 (d, J = 1.3 Hz). 31 P NMR (162 MHz, CDC13) δ 28.0. HRMS (ESI-MS) m / z calcd for C 17 H 28 N2OP[M+H] + : 307.1934, found: 307.1930.

[0172]

[0173] diphenyl(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)phosphine oxide (2a): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1 : 1) as eluent, 87.8 mg, 99% yield, 98% ee, white solid, m.p. 159-160 °C. 1 H NMR (400 MHz, CDC13) δ 7.91 - 7.87 (m, 2H), 7.52 - 7.41 (m, 7H), 7.32 (t, J = 7.2 Hz, 1H), 7.26 - 7.22 (m, 2H), 7.18 - 7.10 (m, 3H), 6.68 (br, 1H), 6.11 (t, J = 2.4 Hz, 1H), 4.63 (d, J = 7.6 Hz, 1H), 1.15 (s, 6H), 1.10 (s, 6H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 137.0 (d, J = 5.2 Hz), 135.9 (d, J = 9.2 Hz), 133.9 (d, J = 4.8 Hz), 132.9 (d, J = 4.6 Hz), 131.381 (d, J = 1.7 Hz), 131.379 (dd, J = 44.3, 8.7 Hz), 130.2 (d, J = 6.7 Hz), 128.251, 128.250 (dd, J = 34.7, 11.5 Hz), 126.7, 84.0, 47.6 (d, J = 66.2 Hz), 24.9, 24.6. 31 P NMR (162 MHz, CDC13) δ 31.0.[α] D 20 = -83.3 (c = 1.5, CHCl3). HRMS (ESI-MS) m / z calcd for C 27 H 31 BO3P[M+H] + : 445.2103, found: 445.2118. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 13.4 min (minor), 20.0 min (major).

[0174]

[0175] (1-(4-fluorophenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)diphenylphosphine oxide (2b): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 83.2 mg, 90% yield, 97% ee, white solid, m.p. 196-197 °C. 1 H NMR (400 MHz, CDC13) δ 7.90 - 7.85 (m, 2H), 7.51 - 7.44 (m, 5H), 7.37 - 7.32 (m, 3H), 7.27 - 7.24 (m, 2H), 6.85 (t, J = 8.8 Hz, 2H), 6.64 (br, 1H), 6.09 - 6.08 (m, 1H), 4.61 (d, J = 6.8 Hz, 1H), 1.15 (s, 6H), 1.09 (s, 6H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 161.9 (d, J = 246.2 Hz), 135.8 (d, J = 8.7 Hz), 133.7 (d, J = 17.8 Hz), 132.8, 132.6 (d, J = 3.8 Hz), 131.8, 131.7, 131.6, 131.5, 131.3, 131.1 (d, J = 8.6 Hz), 128.3 (d, J = 32.1, 11.3 Hz), 115.1 (d, J = 21.3 Hz), 84.1, 47.0 (d, J = 66.4 Hz), 24.9, 24.6. 31 P NMR (162 MHz, CDC13) δ 32.6. 19 F NMR (376 MHz, CDC13) δ -116.2.[α] D 20 = -53.3 (c = 1.5, CHCl3). HRMS (ESI-MS) m / z calcd for C 27 H 30 BFO3PNa [M + Na] +485.1828, found: 485.1830. HPLC (AD-H, n-hexane / isopropanol = 90 / 30, flow rate = 1.0 mL / min, l = 220 nm) tR= 6.5 min (minor), 8.8 min (major).

[0176]

[0177] (1-(4-chlorophenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)diphenylphosphine oxide (2c): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1 : 1) as eluent, 91.9 mg, 96% yield, 97% ee, yellow solid, m.p. 179-180 °C. 1 H NMR (400 MHz, CDC13) δ 7.89 - 7.84 (m, 2H), 7.53 - 7.42 (m, 5H), 7.36 - 7.33 (m, 3H), 7.29 - 7.25 (m, 2H), 7.13 (d, J = 8.4 Hz, 2H), 6.64 - 6.63 (m, 1H), 6.10 - 6.09 (m, 1H), 4.60 (d, J = 7.6 Hz, 1H), 1.15 (s, 6H), 1.09 (s, 6H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 136.1 (d, J = 9.0 Hz), 135.5 (d, J = 5.2 Hz), 133.6 (d, J = 9.5 Hz), 132.7, 132.6 (d, J = 9.5 Hz), 131.6, 131.5, 131.41, 131.37, 131.1 (d, J = 8.6 Hz), 128.40, 128.39 (dd, J = 25.8, 11.7 Hz), 84.1, 47.1 (d, J = 66.2 Hz), 24.9, 24.6. 31 P NMR (162 MHz, CDC13) δ 32.0.[α] D 20 = -70.0 (c = 1.0, CHCl3). HRMS (ESI-MS) m / z calcd for C 27 H 30 BClO3P[M+H]+ : 479.1713, found: 479.1704. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 16.2 min (minor), 39.9 min (major).

[0178]

[0179] (1-(4-bromophenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)diphenylphosphine oxide (2d): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 103.6 mg, 99% yield, 96% ee, white solid, m.p. 183-184 °C. 1 H NMR (400 MHz, CDC13) δ 7.86 - 7.81 (m, 2H), 7.51 - 7.40 (m, 5H), 7.33 (t, J = 7.2 Hz, 1H), 7.26 - 7.14 (m, 6H), 6.61 (br, 1H), 6.08 - 6.07 (m, 1H), 4.58 (d, J = 6.8 Hz, 1H), 1.13 (s, 6H), 1.07 (s, 6H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 136.13 (d, J = 3.7 Hz), 136.06, 133.5 (d, J = 7.7 Hz), 132.5 (d, J = 7.9 Hz), 131.8 (d, J = 6.6 Hz), 131.55, 131.46, 131.3, 131.1 (d, J = 8.7 Hz), 128.4 (d, J = 23.9, 11.5 Hz), 120.9 (d, J = 1.5 Hz), 84.1, 47.1 (d, J = 66.0 Hz), 24.9, 24.6. 31 P NMR (162 MHz, CDC13) δ 32.2.[α] D 20 = -75.0 (c = 2.0, CHCl3). HRMS (ESI-MS) m / z calcd for C 27 H 29 BBrO3PNa[M+Na]+ 547.1011, found: 547.1010. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 17.0 min (minor), 50.5 min (major).

[0180]

[0181] diphenyl(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(p-tolyl)allyl)phosphine oxide (2e): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 69.7 mg, 76% yield, 98% ee, white solid, m.p. 155-156 °C. 1 H NMR (400 MHz, CDC13) δ 7.89 - 7.85 (m, 2H), 7.56 - 7.40 (m, 5H), 7.34 - 7.31 (m, 3H), 7.27 - 7.23 (m, 2H), 6.97 (d, J = 8.0 Hz, 2H), 6.65 - 6.63 (m, 1H), 6.10 - 6.08 (m, 1H), 4.63 (d, J = 7.6 Hz, 1H), 2.24 (s, 3H), 1.15 (s, 6H), 1.10 (s, 6H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 136.3, 135.9 (d, J = 9.3 Hz), 133.8 (d, J = 4.7 Hz), 132.8 (d, J = 2.1 Hz), 131.37 (dd, J = 38.5, 8.8 Hz), 131.35 (d, J = 1.3 Hz), 129.9 (d, J = 6.7 Hz), 129.0, 128.4 (d, J = 11.5 Hz), 128.1 (d, J = 11.5 Hz), 84.0, 47.0 (d, J = 66.7 Hz), 24.9, 24.6, 21.1. 31 P NMR (162 MHz, CDC13) δ 32.3.[α] D 20 = -160.0 (c = 1.0, CHCl3). HRMS (ESI-MS) m / z calcd for C 28H 33 BO3P[M+H] + : 459.2260, found: 459.2263. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 14.0 min (minor), 46.1 min (major).

[0182]

[0183] (1-(4-methoxyphenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)diphenylphosphine oxide (2f): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1 : 1) as eluent, 85.4 mg, 90% yield, 97% ee, white solid, m.p. 156-157 °C. 1 H NMR (400 MHz, CDC13) δ 7.89 - 7.85 (m, 2H), 7.52 - 7.41 (m, 5H), 7.35 - 7.31 (m, 3H), 7.27 - 7.24 (m, 2H), 6.71 (d, J = 8.4 Hz, 2H), 6.63 - 6.61 (m, 1H), 6.08 - 6.07 (m, 1H), 4.59 (d, J = 7.6 Hz, 1H), 3.72 (s, 3H), 1.15 (s, 6H), 1.09 (s, 6H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 158.4, 135.5 (d, J = 9.2 Hz), 133.9 (d, J = 9.4 Hz), 133.0 (d, J = 8.1 Hz), 131.6 (d, J = 8.6 Hz), 131.4, 131.2, 131.1, 128.8 (d, J = 4.9 Hz), 128.3 (d, J = 30.9, 11.3 Hz), 113.7, 84.0, 55.2, 46.7 (d, J = 66.8 Hz), 24.9, 24.7. 31 P NMR (162 MHz, CDC13) δ 32.8.[α] D 20= -100.0 (c = 1.0, CHCI3). HRMS (ESI-MS) m / z calcd for C 28 H 33 BO4P[M+H] + : 475.2210, found: 475.2210. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 20.7 min (minor), 54.5 min (major).

[0184]

[0185] diphenyl(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(4-(trifluoromethoxy)phen- yl)allyl-1)phosphine oxide (2g): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1 : 1) as eluent, 88.8 mg, 84% yield, 96% ee, white solid, m.p. 142-143 °C. 1 H NMR (400 MHz, CDCI3) δ 7.90-7.86 (m, 2H), 7.51-7.45 (m, 5H), 7.40 (d, J = 8.4 Hz, 2H), 7.36-7.32 (m, 1 H), 7.27-7.23 (m, 2H), 7.00 (d, J = 8.4 Hz, 2H), 6.67-6.66 (m, 1 H), 6.1 1-6.10 (m, 1 H), 4.62 (d, J = 7.2 Hz, 1 H), 1.16 (s, 6H), 1.09 (s, 6H). 13 C{ 1 H} NMR (101 MHz, CDCI3) δ 148.2, 136.0 (d, J = 8.8 Hz), 135.6 (d, J = 4.9 Hz), 133.5 (d, J = 24.5 Hz), 132.5 (d, J = 24.0 Hz), 131.6, 131.53, 131.48, 131.4, 131.1 (d, J = 8.5 Hz), 128.4 (dd, J = 34.7, 1 1.3 Hz), 121.8, 120.6, 1 19.2, 84.1, 47.2 (d, J = 66.1 Hz), 24.9, 24.6. 31P NMR (162 MHz, CDC13) δ 32.2. 19 F NMR (376 MHz, CDC13) δ -57.9.[α] D 20 = -100.0 (c = 1.5, CHCI3). HRMS (ESI-MS) m / z calcd for C 28 H 29 BF3O4PNa [M + Na] + : 551.1746, found: 551.1749. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 13.0 min (minor), 39.8 min (major).

[0186]

[0187] methyl 4-(1-(diphenylphosphoryl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)benzoate (2h): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 90.4 mg, 90% yield, 77% ee, white solid, m.p. 173-174 °C. 1 H NMR (400 MHz, CDC13) δ 7.90-7.85 (m, 2H), 7.83 (d, J = 8.0 Hz, 2H), 7.51-7.43 (m, 7H), 7.35-7.31 (m, 1H), 7.26-7.22 (m, 2H), 6.69-6.68 (m, 1H), 6.13-6.11 (m, 1H), 4.68 (d, J = 7.2 Hz, 1H), 3.85 (s, 3H), 1.14 (s, 6H), 1.09 (s, 6H). 13 C{ 1H}NMR (101 MHz, CDC13) δ 167.2, 142.5 (d, J = 4.9 Hz), 136.4 (d, J = 8.9 Hz), 133.4 (d, J = 5.4 Hz), 132.5 (d, J = 5.4 Hz), 131.6, 131.5, 131.4 (d, J = 1.4 Hz), 131.1 (d, J = 8.8 Hz), 130.2 (d, J = 6.2 Hz), 129.5, 128.4 (dd, J = 28.9, 11.4 Hz), 84.1, 52.1, 47.9 (d, J = 65.4 Hz), 24.9, 24.6. 31 P NMR (162 MHz, CDC13) δ 31.4.[α] D 20 = -20.0 (c = 2.0, CHCl3). HRMS (ESI-MS) m / z calcd for C 29 H 32 BO5PNa[M+Na] + : 525.1978, found: 525.1975. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 25.1 min (minor), 51.2 min (major).

[0188]

[0189] diphenyl(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(4-(trifluoromethyl)phenyl)allyl)-phosphi ne oxide(2i): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 92.2 mg, 90% yield, 83% ee, white solid, m.p. 149-150 °C. 1H NMR (400 MHz, CDC13) δ 7.90 - 7.85 (m, 2H), 7.54 - 7.45 (m, 7H), 7.41 (d, J = 8.4 Hz, 2H), 7.34 (t, J = 6.8 Hz, 1H), 7.28 - 7.25 (m, 2H), 6.69 - 6.67 (m, 1H), 6.14 - 6.12 (m, 1H), 4.69 (d, J = 7.6 Hz, 1H), 1.15 (s, 6H), 1.10 (s, 6H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 141.2 (d, J = 4.4 Hz), 136.5 (d, J = 8.7 Hz), 133.3 (d, J = 9.1 Hz), 132.4 (d, J = 9.9 Hz), 131.65, 131.56, 131.5, 131.0 (d, J = 8.6 Hz), 130.4 (d, J = 6.3 Hz), 128.5 (dd, J = 26.2, 11.5 Hz), 125.1 (d, J = 3.5 Hz), 84.2, 47.6 (d, J = 65.7 Hz), 24.9, 24.6. 31 P NMR (162 MHz, CDC13) δ 32.0. 19 F NMR (376 MHz, CDC13) δ -62.5.[α] D 20 = -90.0 (c = 2.0, CHCl3). HRMS (ESI-MS) m / z calcd for C 28 H 29 BF3O3PNa [M + Na] + : 535.1797, found: 535.1791. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 12.9 min (minor), 29.6 min (major).

[0190]

[0191] 4-(1-(diphenylphosphoryl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)benzonitrile (2j): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1 : 1) as eluent, 71.3 mg, 76% yield, 66% ee, white solid, m.p. 172-173 °C. 1 H NMR (400 MHz, CDC13) δ 7.89 - 7.84 (m, 2H), 7.50 - 7.43 (m, 9H), 7.38 - 7.34 (m, 1H), 7.29 - 7.25 (m, 2H), 6.68 - 6.67 (m, 1H), 6.14 - 6.12 (m, 1H), 4.65 (d, J = 7.6 Hz, 1H), 1.15 (s, 6H), 1.08 (s, 6H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 142.6 (d, J = 5.4 Hz), 136.6 (d, J = 8.9 Hz), 133.0 (d, J = 22.1 Hz), 132.2, 131.9, 131.7 (dd, J = 18.1, 1.4 Hz), 131.4 (d, J = 8.8 Hz), 130.9 (d, J = 18.0 Hz), 130.87 (d, J = 2.5 Hz), 128.5 (dd, J = 26.0, 11.6 Hz), 119.0, 110.6, 84.2, 48.0 (d, J = 64.9 Hz), 24.9, 24.6. 31 P NMR (162 MHz, CDC13) δ 31.3.[α] D 20 = -112.0 (c = 2.5, CHCl3). HRMS (ESI-MS) m / z calcd for C 28 H 30 BNO3P[M+H] + : 470.2056, found: 470.2052. HPLC (AD-H, n-hexane / isopropanol = 70 / 30, flow rate = 1.0 mL / min, l = 220 nm) tR= 8.0 min (minor), 15.9 min (major).

[0192]

[0193] (1-(3-chloro-4-fluorophenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)diphenylphosphine oxide (2k): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 98.4 mg, 99% yield, 95% ee, white solid, m.p. 159-160 °C. 1 H NMR (400 MHz, CDC13) δ 7.85 (dd, J = 10.8, 7.2 Hz, 2H), 7.53 - 7.43 (m, 5H), 7.38 - 7.26 (m, 5H), 6.93 (t, J = 8.8 Hz, 1H), 6.64 (br, 1H), 6.11 - 6.10 (m, 1H), 4.56 (d, J = 4.0 Hz, 1H), 1.16 (s, 6H), 1.11 (s, 6H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 157.2 (d, J = 249.1 Hz), 136.3 (d, J = 8.1 Hz), 134.0, 133.3 (d, J = 16.6 Hz), 132.4 (d, J = 17.4 Hz), 132.1 (d, J = 5.9 Hz), 131.55 (d, J = 19.3 Hz), 131.53, 131.1 (d, J = 8.3 Hz), 129.9, 129.81, 129.75, 128.5 (dd, J = 23.4, 11.4 Hz), 120.4 (d, J = 17.8 Hz), 116.2 (d, J = 21.0 Hz), 84.2, 46.9 (d, J = 64.1 Hz), 24.9, 24.6. 31 P NMR (162 MHz, CDC13) δ 31.4. 19 F NMR (376 MHz, CDC13) δ -118.4.[α] D 20 = -45.0 (c = 2.0, CHCl3). HRMS (ESI-MS) m / z calcd for C 27 H 29 BClFO3P[M+H] +: 497.1619, found: 497.1621. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 14.2 min (minor), 22.2 min (major).

[0194]

[0195] (1-(3-methoxyphenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)diphenylphosphine oxide (21): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1 : 1) as eluent, 76.8 mg, 81% yield, 93% ee, white solid, m.p. 81-82 °C. 1 H NMR (400 MHz, CDC13) δ 7.89 - 7.85 (m, 2H), 7.56 - 7.51 (m, 2H), 7.48 - 7.41 (m, 3H), 7.34 - 7.31 (m, 1H), 7.27 - 7.23 (m, 2H), 7.09 - 6.99 (m, 3H), 6.69 - 6.65 (m, 2H), 6.11 (dd, J = 3.2, 2.4 Hz, 1H), 4.61 (d, J = 7.6 Hz, 1H), 3.68 (s, 3H), 1.15 (s, 6H), 1.10 (s, 6H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 159.3, 138.5 (d, J = 4.9 Hz), 136.0 (d, J = 8.9 Hz), 133.9 (d, J = 5.6 Hz), 132.9 (d, J = 5.4 Hz), 131.6 (d, J = 8.7 Hz), 131.4, 131.22, 131.17, 131.1, 129.1, 128.3 (dd, J = 29.8, 11.5 Hz), 122.6 (d, J = 6.8 Hz), 115.2 (d, J = 6.8 Hz), 112.9, 84.0, 55.2, 47.5 (d, J = 66.4 Hz), 24.9, 24.6. 31 P NMR (162 MHz, CDC13) δ 32.9.[α] D 20= -63.6 (c = 2.2, CHCl3). HRMS (ESI-MS) m / z calcd for C 28 H 32 BO4PNa[M+Na] + :497.2028, found:497.2023. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 23.4 min (minor), 49.1 min (major).

[0196]

[0197] (1-(2-chlorophenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)diphenylphosphine oxide (2m): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 50.7 mg, 53% yield, 76% ee, white oil. 1 H NMR (400 MHz, CDC13) δ 8.21 (d, J = 7.6 Hz, 1H), 7.88 - 7.83 (m, 2H), 7.61 - 7.57 (m, 2H), 7.49 - 7.42 (m, 3H), 7.36 - 7.33 (m, 1H), 7.28 - 7.25 (m, 2H), 7.20 - 7.14 (m, 2H), 7.05 (t, J = 7.6 Hz, 1H), 6.46 - 6.44 (m, 1H), 6.18 (dd, J = 4.0, 2.0 Hz, 1H), 5.32 (d, J = 8.0 Hz, 1H), 1.08 (s, 6H), 1.03 (s, 6H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 137.3 (d, J = 8.5 Hz), 136.1, 134.1 (d, J = 9.1 Hz), 133.5 (d, J = 9.2 Hz), 132.5 (d, J = 7.5 Hz), 132.0, 131.9, 131.4 (d, J = 4.0 Hz), 131.1 (d, J = 8.8 Hz), 129.2, 128.3 (dd, J = 11.5, 5.1 Hz), 128.0, 127.0, 83.9, 43.0 (d, J = 66.9 Hz), 25.2, 24.2.31 P NMR (162 MHz, CDC13) δ 32.0.[α] D 20 = +40.0 (c = 2.5, CHCI3). HRMS (ESI-MS) m / z calcd for C 27 H 29 BCI03PNa [M + Na] + : 501.1533, found: 501.1532. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 20.4 min (minor), 31.6 min (major).

[0198]

[0199] (1-(2-iodophenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)diphenylphosphine oxide (2n): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 58.2 mg, 51% yield, 89% ee, white solid, m.p. 137-138 °C. 1 H NMR (400 MHz, CDC13) δ 8.22 (d, J = 7.6 Hz, 1H), 7.90-7.86 (m, 2H), 7.68 (d, J = 7.6 Hz, 1H), 7.56-7.45 (m, 5H), 7.35 (t, J = 7.2 Hz, 1H), 7.28-7.24 (m, 3H), 6.81 (t, J = 7.6 Hz, 1H), 6.44 (br, 1H), 6.20 (br, 1H), 5.13 (d, J = 8.4 Hz, 1H), 1.08 (s, 6H), 1.05 (s, 6H). 13 C{ 1H}NMR (101 MHz, CDC13) δ 140.8, 139.5, 137.2 (d, J = 8.5 Hz), 132.3 (d, J = 9.9 Hz), 132.0 (d, J = 8.7 Hz), 131.8 (d, J = 4.3 Hz), 131.5, 131.4, 131.3, 128.5, 128.4, 128.3, 128.2, 103.1 (d, J = 10.4 Hz), 83.9, 51.2 (d, J = 65.4 Hz), 25.3, 24.3. 31 P NMR (162 MHz, CDC13) δ 32.3.[α] D 20 = +32.0 (c = 2.5, CHCl3). HRMS (ESI-MS) m / z calcd for C 27 H 29 BIO3PNa[M+Na] + : 593.0889, found: 593.0887. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 13.6 min (minor), 19.8 min (major).

[0200]

[0201] (1-(naphthalen-1-yl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)diphenylphosphine oxide (2o): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 59.3 mg, 60% yield, 44% ee, white solid, m.p. 154-155 °C. 1H NMR (400 MHz, CDC13) δ 8.46 (d, J = 5.6 Hz, 1H), 8.35 (d, J = 8.0 Hz, 1H), 7.85 - 7.78 (m, 3H), 7.66 - 7.64 (m, 3H), 7.48 - 7.44 (m, 5H), 7.35 (t, J = 6.8, 1H), 7.27 - 7.24 (m, 1H), 7.19 - 7.17 (m, 2H), 6.45 (br, 1H), 6.23 (br, 1H), 5.52 (d, J = 8.0 Hz, 1H), 1.09 (s, 6H), 1.07 (s, 6H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 138.3 (d, J = 5.8 Hz), 135.7, 134.0, 132.1 (d, J = 8.1 Hz), 131.8 (d, J = 8.2 Hz), 131.3 (d, J = 2.3 Hz), 131.1 (d, J = 7.6 Hz), 129.0, 128.4, 128.3, 128.2, 128.0 (d, J = 4.4 Hz), 127.3, 125.9, 125.7 (d, J = 54.8 Hz), 84.0, 41.7 (d, J = 63.8 Hz), 25.3, 24.2. 31 P NMR (162 MHz, CDC13) δ 32.3.[α] D 20 = +26.9 (c = 2.6, CHCl3). HRMS (ESI-MS) m / z calcd for C 31 H 32 BO3PNa[M+Na] + : 517.2080, found: 517.2081. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 23.8 min (minor), 29.2 min (major).

[0202]

[0203] diphenyl(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(thiophen-3-yl)allyl)phosphine oxide (2p): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 85.6 mg, 95% yield, 94% ee, white solid, m.p. 144-145 °C. 1 H NMR (400 MHz, CDC13) δ 7.84 (t, J = 8.4 Hz, 2H), 7.57 (m, 2H), 7.49-7.39 (m, 3H), 7.36 (d, J = 7.2 Hz, 1H), 7.31-7.26 (m, 3H), 7.14-7.12 (m, 1H), 7.06 (d, J = 4.8 Hz, 1H), 6.56 (br, 1H), 6.14-6.13 (m, 1H), 4.84 (d, J = 7.2 Hz, 1H), 1.15 (s, 6H), 1.10 (s, 6H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 136.7 (d, J = 5.8 Hz), 136.3 (d, J = 8.8 Hz), 133.7 (d, J = 34.9 Hz), 132.7 (d, J = 34.8 Hz), 131.4 (dd, J = 53.8, 8.8 Hz), 131.37 (dd, J = 15.4, 1.2 Hz), 129.2 (d, J = 5.5 Hz), 128.3 (dd, J = 20.0, 10.5 Hz), 124.9, 123.7 (d, J = 7.7 Hz), 84.0, 43.1 (d, J = 66.9 Hz), 24.9, 24.7. 31 P NMR (162 MHz, CDC13) δ 32.1.[α] D 20 = -66.7 (c = 1.5, CHCl3). HRMS (ESI-MS) m / z calcd for C 25 H 29 BO3PS[M+H] +:451.1667, found: 451.1666. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 16.0 min (minor), 20.3 min (major).

[0204]

[0205] diphenyl(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(thiophen-2-yl)allyl)phosphine oxide (2q): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1 : 1) as eluent, 76.5 mg, 85% yield, 81% ee, brown solid, m.p. 148-149 °C. 1 H NMR (400 MHz, CDC13) δ 7.87 - 7.82 (m, 2H), 7.68 - 7.63 (m, 2H), 7.48 - 7.38 (m, 4H), 7.35 - 7.31 (m, 2H), 7.07 - 7.06 (m, 2H), 6.82 (t, J = 4.4 Hz, 1H), 6.64 - 6.62 (m, 1H), 6.19 - 6.18 (m, 1H), 4.97 (d, J = 8.8 Hz, 1H), 1.15 (s, 6H), 1.11 (s, 6H). 13 C{ 1 H}NMR (101 MHz, CDC13) δ 139.0 (d, J = 5.8 Hz), 136.9 (d, J = 8.5 Hz), 133.3 (d, J = 7.9 Hz), 132.3 (d, J = 7.4 Hz), 131.5 (dd, J = 43.0, 8.8 Hz), 131.3 (dd, J = 7.7, 1.8 Hz), 128.3 (dd, J = 14.4, 11.8 Hz), 127.3 (d, J = 6.5 Hz), 126.8, 124.7 (d, J = 1.1 Hz), 84.1, 42.5 (d, J = 66.2 Hz), 24.9, 24.6. 31 P NMR (162 MHz, CDC13) δ 30.9.[α] D 20= -66.7 (c = 1.5, CHCI3). HRMS (ESI-MS) m / z calcd for C 25 H 28 BO3PSNa[M+Na] + : 473.1482, found: 473.1452. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 21.1 min (minor), 29.0 min (major).

[0206]

[0207] diphenyl(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-2-yl)phosphine oxide (2r): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 52 mg, 68% yield, 79% ee, white oil. 1 HNMR (400 MHz, CDCI3) δ 7.89-7.84 (m, 2H), 7.76-7.71 (m, 2H), 7.47-7.44 (m, 3H), 7.42-7.33 (m, 3H), 6.23-6.21 (m, 1H), 6.1 1-6.09 (m, 1H), 3.53-3.46 (m, 1H), 1.32 (dd, J = 16.4, 7.6 Hz, 3H), 1.1 1 (s, 6H), 1.08 (s, 6H). 13 C{ 1 H}NMR (101 MHz, CDCI3) δ 134.9 (d, J = 8.7 Hz), 133.6 (d, J = 37.7 Hz), 132.6 (d, J = 33.8 Hz), 131.45 (dd, J = 27.1, 8.8 Hz), 131.35 (dd, J = 24.6, 1.4 Hz), 128.4 (dd, J = 35.8, 1 1.0 Hz), 83.8, 35.0 (d, J = 67.4 Hz), 24.9, 24.7, 15.1 (d, J = 2.4 Hz). 31 P NMR (162 MHz, CDCI3) δ 34.1.[α] D 20= + 32.0 (c = 2.5, CHCI3). HRMS (ESI-MS) m / z calcd for C 22 H 29 BO3P[M+H] + : 383.1946, found: 383.1944. HPLC (IC, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 31.3 min (minor), 39.3 min (major).

[0208]

[0209] bis(4-fluorophenyl)(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)phosphine oxide (4a): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 79.7 mg, 83% yield, 96% ee, white oil. 1 H NMR (400 MHz, CDCI3) δ 7.90 - 7.83 (m, 2H), 7.49 - 7.43 (m, 2H), 7.39 - 7.37 (m, 2H), 7.20 - 7.12 (m, 5H), 6.94 (dt, J = 8.6, 2.0 Hz, 2H), 6.65 - 6.64 (m, 1H), 6.12 - 6.11 (m, 1H), 4.55 (d, J = 7.6 Hz, 1H), 1.16 (s, 6H), 1.11 (s, 6H). 13 C{ 1 H} NMR (101 MHz, CDCI3) δ 136.5 (d, J = 5.6 Hz), 136.2 (d, J = 9.4 Hz), 134.1, 134.0, 133.9, 133.7, 133.6, 133.5, 130.1 (d, J = 6.8 Hz), 128.4, 127.0, 116.1, 115.94, 115.85, 115.7, 115.6, 115.5, 115.4, 84.1, 47.9 (d, J = 67.4 Hz), 24.9, 24.6. 31 P NMR (162 MHz, CDCI3) δ 31.3. 19F NMR (376 MHz, CDC13) δ -107.5, -107.6.[α] D 20 = -60.0 (c = 1.5, CHCl3). HRMS (ESI-MS) m / z calcd for C 27 H 29 BF2O3P [M + H] + : 481.1915, found: 481.1918. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 12.1 min (minor), 26.5 min (major).

[0210]

[0211] bis(3,5-dimethylphenyl)(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)phosphine oxide (4b): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 79.1 mg, 79% yield, 92% ee, white solid, m.p. 77-78 °C. 1 H NMR (400 MHz, CDC13) δ 7.46 (d, J = 11.2 Hz, 2H), 7.39 (d, J = 8.0 Hz, 2H), 7.18 - 7.09 (m, 4H), 7.03 (d, J = 11.6 Hz, 2H), 6.92 (s, 1H), 6.67 (br, 1H), 6.10 (t, J = 2.8 Hz, 1H), 4.55 (d, J = 7.6 Hz, 1H), 2.34 (s, 6H), 2.16 (s, 6H), 1.16 (s, 6H), 1.09 (s, 6H). 13 C{ 1H}NMR (101 MHz, CDC13) δ 137.7 (dd, J = 42.2, 12.0 Hz), 137.2 (d, J = 5.1 Hz), 135.7 (d, J = 9.0 Hz), 133.6 (d, J = 15.2 Hz), 133.0 (dd, J = 30.9, 2.3 Hz), 132.7 (d, J = 14.4 Hz), 130.2 (d, J = 6.5 Hz), 129.0 (dd, J = 35.5, 8.8 Hz), 128.1, 126.6, 83.9, 47.7 (d, J = 65.8 Hz), 25.0, 24.4, 21.5, 21.3. 31 P NMR (162 MHz, CDC13) δ 33.2.[α] D 20 = -80.0 (c = 2.0, CHCl3). HRMS (ESI-MS) m / z calcd for C 31 H 39 BO3P[M+H] + : 501.2730, found: 501.2725. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 6.5 min (minor), 10.4 min (major).

[0212]

[0213] (1-(4-bromophenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)bis(3,5-dimet-hylphe-nyl)phosphine oxide (4c): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 76.5 mg, 66% yield, 96% ee, green solid, m.p. 79-80 °C. 1H NMR (400 MHz, CDC13) δ 7.41 (d, J = 11.2 Hz, 2H), 7.28 - 7.26 (m, 2H), 7.25 - 7.22 (m, 2H), 7.08 (s, 1H), 7.02 (d, J = 11.6 Hz, 2H), 6.94 (s, 1H), 6.63 (br, 1H), 6.08 (t, J = 2.8 Hz, 1H), 4.48 (d, J = 7.6 Hz, 1H), 2.32 (s, 6H), 2.18 (s, 6H), 1.15 (s, 6H), 1.08 (s, 6H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 137.9 (dd, J = 31.5, 12.2 Hz), 136.3 (d, J = 5.1 Hz), 136.0 (d, J = 9.2 Hz), 133.25 (d, J = 20.0 Hz), 133.18 (dd, J = 22.2, 2.4 Hz), 132.3 (d, J = 20.2 Hz), 131.9 (d, J = 6.5 Hz), 131.2, 128.9 (dd, J = 39.3, 8.9 Hz), 120.8, 84.0, 47.1 (d, J = 65.5 Hz), 25.0, 24.5, 21.5, 21.4. 31 P NMR (162 MHz, CDC13) δ 32.9.[α] D 20 = -77.3 (c = 2.2, CHCl3). HRMS (ESI-MS) m / z calcd for C 31 H 38 BBr03P [M + H] + : 579.1835, found: 579.1830. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 7.0 min (minor), 14.0 min (major).

[0214]

[0215] bis(3-methoxyphenyl)(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(p-tolyl)allyl)phosphine oxide (4d): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v=1:1) as eluent, 55 mg, 53% yield, 94% ee, white solid, m.p. 71-72 °C. 1 H NMR (400 MHz, CDC13) δ 7.44 - 7.30 (m, 5H), 7.17 (dt, J = 8.0, 4.0 Hz, 1H), 7.07 - 6.98 (m, 5H), 6.86 (dd, J = 8.0, 2.0 Hz, 1H), 6.64 (br, 1H), 6.08 (dd, J = 3.2, 2.4 Hz, 1H), 4.55 (d, J = 8.0 Hz, 1H), 3.82 (s, 3H), 3.62 (s, 3H), 2.25 (s, 3H), 1.15 (s, 6H), 1.10 (s, 6H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 159.3 (dd, J = 45.7, 14.0 Hz), 136.6 (d, J = 50.4 Hz), 135.6 (d, J = 9.5 Hz), 135.1 (d, J = 24.5 Hz), 134.2 (d, J = 23.9 Hz), 133.9 (d, J = 5.7 Hz), 130.0 (d, J = 6.7 Hz), 129.4 (dd, J = 31.2, 13.8 Hz), 129.0, 123.4 (dd, J = 38.2, 9.1 Hz), 117.7, 116.3 (dd, J = 59.8, 9.2 Hz), 84.0, 55.4 (d, J = 19.5 Hz), 47.2 (d, J = 66.8 Hz), 25.0, 24.6, 21.1. 31 P NMR (162 MHz, CDC13) δ 32.9.[α] D 20 = -40.9 (c = 2.2, CHCl3). HRMS (ESI-MS) m / z calcd for C 30 H 37 BO5P[M+H] +:519.2472, found: 519.2471. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 22.8 min (minor), 53.6 min (major).

[0216]

[0217] bis(2-methoxyphenyl)(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)phosphine oxide (4e): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1 : 1) as eluent, 55.5 mg, 55% yield, 88% ee, white solid, m.p. 81-82 °C. 1 H NMR (400 MHz, CDC13) δ 7.91 (ddd, J = 12.8, 7.6, 1.2 Hz, 1H), 7.58 (ddd, J = 12.4, 7.6, 1.2 Hz, 1H), 7.44 (d, J = 7.6 Hz, 2H), 7.40 - 7.36 (m, 1H), 7.26 - 7.22 (m, 1H), 7.13 - 7.09 (m, 2H), 7.06 - 6.97 (m, 2H), 6.81 - 6.77 (m, 2H), 6.67 - 6.64 (m, 2H), 6.05 - 6.03 (m, 1H), 5.10 (d, J = 10.0 Hz, 1H), 3.67 (s, 3H), 3.53 (s, 3H), 1.17 (s, 6H), 1.08 (s, 6H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 160.3 (dd, J = 67.3, 3.3 Hz), 138.4 (d, J = 5.2 Hz), 134.5 (dd, J = 12.5, 9.8 Hz), 134.2 (d, J = 6.1 Hz), 132.8, 132.6 (d, J = 1.0 Hz), 130.2 (d, J = 7.0 Hz), 127.8, 126.2, 123.0, 122.0, 120.3 (d, J = 11.2 Hz), 110.8 (dd, J = 33.6, 6.7 Hz), 83.6, 55.3 (d, J = 8.3 Hz), 46.8 (d, J = 70.1 Hz), 25.2, 24.4.31 PNMR (162 MHz, CDC13) δ 31.1. [α] D 20 = -66.7 (c = 1.5, CHCl3). HRMS (ESI-MS) m / z calcd for C 29 H 35 BO5P[M+H] + : 505.2315, found: 505.2323. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 21.8 min (minor), 33.5 min (major).

[0218]

[0219] (1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)di-o-tolylphosphine oxide (4f): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 47.2 mg, 50% yield, 78% ee, yellow solid, m.p. 75-76 °C. 1 H NMR (400 MHz, CDC13) δ 7.80 (dd, J = 12.0, 7.2 Hz, 1H), 7.41-7.39 (m, 2H), 7.36-7.29 (m, 2H), 7.27-7.11 (m, 6H), 7.01-6.95 (m, 2H), 6.73 (br, 1H), 6.20 (t, J = 3.0 Hz, 1H), 4.66 (d, J = 7.6 Hz, 1H), 2.33 (s, 3H), 2.09 (s, 3H), 1.15 (s, 6H), 1.06 (s, 6H). 13 C{ 1H}NMR (101 MHz, CDC13) δ 142.8 (d, J = 46.2, 7.4 Hz), 137.6 (d, J = 4.9 Hz), 136.5 (d, J = 8.6 Hz), 133.1 (d, J = 10.3 Hz), 132.4 (d, J = 24.8 Hz), 132.0 (dd, J = 13.3, 11.8 Hz), 131.5 (d, J = 10.6 Hz), 131.2 (dd, J = 26.4, 2.0 Hz), 130.4 (d, J = 6.4 Hz), 128.2, 126.6, 125.0 (dd, J = 1.3 Hz), 124.9 (d, J = 2.4 Hz), 83.9, 47.0 (d, J = 66.2 Hz), 25.0, 24.4, 21.5 (d, J = 3.7 Hz), 20.9 (d, J = 3.2 Hz). 31 P NMR (162 MHz, CDC13) δ 37.0.[α] D 20 = -34.6 (c = 2.6, CHCl3). HRMS (ESI-MS) m / z calcd for C 29 H 35 BO3P[M+H] + : 473.2416, found: 473.2421. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 7.3 min (minor), 9.3 min (major).

[0220]

[0221] dicyclohexyl(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)phosphine oxide (4g): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 2:1) as eluent, 59.3 mg, 65% yield, 80% ee, viscous oil. 1H NMR (400 MHz, CDC13) δ 7.54 (d, J = 8.0 Hz, 2H), 7.29 - 7.25 (m, 2H), 7.22 - 7.18 (m, 1H), 6.72 (t, J = 2.0 Hz, 1H), 6.12 (t, J = 2.8 Hz, 1H), 3.97 (d, J = 5.6 Hz, 1H), 2.11 - 1.81 (m, 9H), 1.72 - 1.56 (m, 5H), 1.43 - 1.32 (m, 3H), 1.22 (s, 12H), 1.07 - 0.85 (m, 5H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 139.1 (d, J = 5.2 Hz), 135.5 (d, J = 7.1 Hz), 129.8 (d, J = 6.1 Hz), 129.2 (d, J = 16.7 Hz), 128.6, 126.7, 84.0, 42.9 (d, J = 55.1 Hz), 38.3 (dd, J = 61.3, 9.9 Hz), 27.5, 27.37, 27.35, 27.22, 27.16, 27.13, 27.11, 27.10, 27.04, 26.97, 26.9 (d, J = 2.2 Hz), 26.4 (d, J = 1.0 Hz), 26.2, 25.0, 24.8. 31 P NMR (162 MHz, CDC13) δ 52.2.[α] D 20 = -100.0 (c = 1.5, CHCl3). HRMS (ESI-MS) m / z calcd for C 27 H 43 BO3P[M+H] + : 457.3042, found: 457.3052. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 8.5 min (major), 21.0 min (minor).

[0222]

[0223] diisobutyl(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)phosphine oxide (4h): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 2: 1) as eluent, 42.9 mg, 53% yield, 86% ee, white solid, m.p. 76-77 °C. 1 H NMR (400 MHz, CDC13) δ 7.49-7.47 (m, 2H), 7.30-7.26 (m, 2H), 7.23-7.19 (m, 1H), 6.53 (br, 1H), 6.14 (t, J = 2.8 Hz, 1H), 3.78 (d, J = 8.8 Hz, 1H), 2.19-2.00 (m, 2H), 1.83-1.62 (m, 2H), 1.55-1.41 (m, 2H), 1.21 (s, 6H), 1.19 (s, 6H), 1.06-1.02 (m, 6H), 0.87 (d, J = 11.6, 6.4 Hz, 6H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 138.0 (d, J = 4.8 Hz), 134.5 (d, J = 8.3 Hz), 129.9 (d, J = 6.4 Hz), 129.3 (d, J = 103.7 Hz), 128.5, 126.8, 84.0, 49.6 (d, J = 59.4 Hz), 37.5 (dd, J = 62.4, 43.3 Hz), 25.2 (dd, J = 16.2, 9.6 Hz), 24.9, 24.7, 24.5 (dd, J = 14.8, 7.0 Hz), 23.9 (dd, J = 31.4, 3.7 Hz). 31 P NMR (162 MHz, CDC13) δ 48.0.[α] D 20 = -45.5 (c = 2.2, CHCl3). HRMS (ESI-MS) m / z calcd for C 23 H 39 BO3P[M+H] +:405.2730, found: 405.2727. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 13.2 min (minor), 15.5 min (major).

[0224]

[0225] Dimethyl(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)phosphonate (4i): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 2:1) as eluent, 32 mg, 45% yield, 94% ee, green oil. 1 HNMR (400 MHz, CDC13) δ 7.44-7.42 (m, 2H), 7.31-7.26 (m, 2H), 7.24-7.20 (m, 1H), 6.28-6.27 (m, 1H), 6.12-6.10 (m, 1H), 4.24 (d, J = 24.0 Hz, 1H), 3.71 (d, J = 11.2 Hz, 3H), 3.51 (d, J = 10.4 Hz, 3H), 1.20 (s, 6H), 1.14 (s, 6H). 13 C{ 1 H}NMR (101 MHz, CDC13) δ 136.0 (d, J = 5.6 Hz), 133.0 (d, J = 10.0 Hz), 130.0 (d, J = 7.6 Hz), 129.0 (d, J = 22.4 Hz), 128.4, 127.1 (d, J = 1.3 Hz), 84.0, 53.4 (d, J = 6.9 Hz), 53.1 (d, J = 7.0 Hz), 46.8 (d, J = 137.6 Hz), 24.9, 24.6. 31 PNMR (162 MHz, CDC13) δ 29.1.[α] D 20 = -55.6 (c = 1.8, CHCl3). HRMS (ESI-MS) m / z calcd for C 17 H 26 BO5PNa[M+Na] +375.1506, found: 375.1505. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 5.5 min (minor), 6.6 min (major).

[0226]

[0227] diethyl(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)phosphonate (4j): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 2:1) as eluent, 66.9 mg, 88% yield, 95% ee, white oil. 1 HNMR (400 MHz, CDC13) δ 7.44-7.42 (m, 2H), 7.28-7.24 (m, 2H), 7.21-7.17 (m, 1H), 6.33-6.32 (m, 1H), 6.10 (dd, J = 3.6, 2.4 Hz, 2H), 4.19 (d, J = 23.6 Hz, 1H), 4.09-4.01 (m, 2H), 3.94-3.86 (m, 1H), 3.81-3.72 (m, 1H), 1.26 (t, J = 7.2 Hz, 3H), 1.19 (s, 6H), 1.12 (s, 6H), 1.08 (t, J = 6.8 Hz, 3H). 13 C{ 1 H}NMR (101 MHz, CDC13) δ 136.4 (d, J = 5.8 Hz), 132.9 (d, J = 9.8 Hz), 130.0 (d, J = 7.6 Hz), 128.7, 128.3, 126.9 (d, J = 1.7 Hz), 83.9, 62.5 (d, J = 6.9 Hz), 62.2 (d, J = 7.0 Hz), 47.1 (d, J = 137.3 Hz), 24.9, 24.5, 16.5 (d, J = 6.0 Hz), 16.3 (d, J = 5.9 Hz). 31 P NMR (162 MHz, CDC13) δ 26.7.[α] D 20 = -28.0 (c = 2.5, CHCl3). HRMS (ESI-MS) m / z calcd for C 19 H31 BO5P[M+H] + :381.2002, found: 381.2004. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 5.9 min (minor), 7.8 min (major).

[0228]

[0229] (4k): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 2: 1) as eluent, 54.7 mg, 63% yield, 59% ee, white oil. 1 H NMR (400 MHz, CDC13) δ 7.51 - 7.49 (m, 2H), 7.23 - 7.19 (m, 2H), 7.15 - 7.11 (m, 1H), 6.78 - 6.77 (m, 1H), 6.07 - 6.05 (m, 1H), 4.08 (d, J = 13.6 Hz, 1H), 3.08 - 2.98 (m, 4H), 2.75 - 2.67 (m, 4H), 1.18 (s, 6H), 1.15 (s, 6H), 1.08 (t, J = 7.2 Hz, 6H), 0.76 (t, J = 7.2 Hz, 6H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 138.9 (d, J = 4.7 Hz), 134.0 (d, J = 8.0 Hz), 130.3 (d, J = 6.9 Hz), 128.8, 128.0, 126.3, 83.8, 45.1 (d, J = 109.5 Hz), 39.5 (d, J = 3.6 Hz), 38.9 (d, J = 3.4 Hz), 25.0, 24.6, 14.5, 14.3. 31 P NMR (162 MHz, CDC13) δ 34.0.[α] D 20 = -66.7 (c = 1.5, CHCl3). HRMS (ESI-MS) m / z calcd for C 23 H 40 BN2O3PNa[M+Na] +: 457.2766, found: 457.2762. HPLC (IC, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 10.7 min (minor), 11.5 min (major).

[0230] Application Example

[0231] In this application example, compound 2a was subjected to a series of transformations according to the reaction scheme shown in Formula 10. It was found that the derivatization reactions shown in Formula 10 could be carried out smoothly, and the corresponding products were obtained with the configuration reserved. The palladium-catalyzed Suzuki coupling reaction gave product 5 in 92% yield and 97% ee value. Hydrolysis of 2a under CH3B(OH)2 / HCl conditions gave the corresponding boronic acid compound 6 in 63% yield and 97% ee value. Figure 2 The single crystal diffraction structure of compound 6 was analyzed by X-ray diffraction to determine that the chiral center of compound 6 was in the R configuration. Under the action of copper (II) halide, 2a was subjected to high-yield chlorination and bromination in water-containing methanol. The silver-catalyzed deboronation of 2a proceeded smoothly under aerobic conditions.

[0232]

[0233] (1) Specific preparation method of product 5 in Formula 10:

[0234]

[0235] According to the reaction scheme shown in Formula 11, a 25 mL Schlenk tube was added with a magnetic stirrer, vacuumed and replaced with nitrogen, repeated three times, and then added with tetrakis triphenylphosphine palladium (5 mol%), cesium fluoride (2 equiv), 2a (0.1 mmol) and methyl p-iodobenzoate (0.12 mmol) under a nitrogen atmosphere. Solvent 1.4-dioxane (2 mL) / water (0.1 mL) was added, and the reaction was stirred at 90°C overnight. After the reaction was completed, saturated sodium chloride (5 mL) was added to quench the reaction, and the layers were separated by a separatory funnel, and the aqueous phase was extracted with ethyl acetate (5 mL x 3), and the organic phase was combined and finally dried with anhydrous sodium sulfate. The solvent was removed by a rotary evaporator, and the crude product was separated by column chromatography (petroleum ether: ethyl acetate = 1:1, v:v) to obtain the target product 5.

[0236] (2) Specific preparation method of product 6 in Formula 10:

[0237]

[0238] According to the reaction scheme shown in Formula 12, a 25 mL Schlenk tube was added with a magnetic bar, vacuumed and replaced with nitrogen, repeated three times, and then 2a (88.9 mg, 0.2 mmol, 1.0 equiv), methyl boronic acid (5-10 equiv) and hydrochloric acid / acetone (1 mL / 1 mL) were sequentially added. The reaction was stirred at room temperature, after the reaction was completed, deionized water was added, and the layers were separated by standing, the organic phase was separated with a separatory funnel, and the aqueous phase was extracted with ethyl acetate (5 mL x 3), and the combined organic phase was finally dried with anhydrous sodium sulfate. The solvent was removed by a rotary evaporator, the crude product was separated by column chromatography (petroleum ether: ethyl acetate = 1:1, v:v) to obtain the product, and then the pure target product 6 was recrystallized with ethyl acetate and petroleum ether.

[0239] (3) Specific preparation method of products 7 and 8 in Formula 10:

[0240]

[0241] According to the reaction scheme shown in Formula 13, a 25 mL Schlenk tube was added with a magnetic bar, and then 2a (88.9 mg, 0.2 mmol), copper halide (0.6 mmol, X = Cl or Br) and methanol / water (1 mL / 1 mL) were sequentially added, and the reaction was stirred at 80°C for 6 hours. After the reaction was completed, the reaction was quenched with saturated sodium chloride solution (1 mL), the layers were separated by standing, the organic phase was separated with a separatory funnel, and the aqueous phase was extracted with ethyl acetate (5 mL x 3), and the combined organic phase was finally dried with anhydrous sodium sulfate. The solvent was removed by a rotary evaporator, and the crude product was separated by column chromatography (petroleum ether: ethyl acetate = 1:1, v:v) to obtain the target products 7 and 8.

[0242] (3) Specific preparation method of product 9 in Formula 10:

[0243]

[0244] According to the reaction scheme shown in Formula 14, a 25 mL Schlenk tube was added with a magnetic bar, and then 2a (88.9 mg, 0.2 mmol), silver nitrate (2.0 mg, 6 mol%), triethylamine (20.2 mg, 0.2 mmol) and ethanol / water (1 mL / 1 mL) were sequentially added, and the reaction was stirred at 80°C for 3 hours. After the reaction was completed, the reaction was quenched with saturated sodium chloride solution (1 mL), the layers were separated by standing, the organic phase was separated with a separatory funnel, and the aqueous phase was extracted with ethyl acetate (5 mL x 3), and the combined organic phase was finally dried with anhydrous sodium sulfate. The solvent was removed by a rotary evaporator, and the crude product was separated by column chromatography (petroleum ether: ethyl acetate = 1:1, v:v) to obtain the target product 9.

[0245] The structural characterization data of the prepared compounds 5-9 in the application example are specifically as follows:

[0246]

[0247] methyl 4-(3-(diphenylphosphoryl)-3-phenylprop-1-en-2-yl)benzoate (5): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1:1) as eluent, 41.6 mg, 92% yield, 97% ee, yellow solid, m.p. 183-184℃. 1 H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.4 Hz, 2H), 7.81-7.76 (m, 2H), 7.51-7.47 (m, 1H), 7.43-7.35 (m, 5H), 7.31-7.29 (m, 2H), 7.27-7.23 (m, 2H), 7.20-7.18 (m, 5H), 6.39 (d, J = 2.0 Hz, 1H), 5.61 (d, J = 1.6 Hz, 1H), 4.55 (d, J = 9.6 Hz, 1H), 3.88 (s, 3H). 13 C{ 1 H}NMR (101 MHz, CDCl3) δ 166.9, 147.7 (d, J = 8.6 Hz), 143.6 (d, J = 3.4 Hz), 134.5 (d, J = 6.1 Hz), 133.0 (d, J = 7.1 Hz), 132.0 (d, J = 5.4 Hz), 131.7 (dd, J = 23.8, 2.4 Hz), 131.3 (dd, J = 16.5, 8.9 Hz), 130.2 (d, J = 5.4 Hz), 129.8, 129.2, 128.5, 128.4 (dd, J = 43.4, 11.7 Hz), 127.5 (d, J = 1.3 Hz), 126.3, 121.4 (d, J = 7.1 Hz), 52.3, 51.6. 31 P NMR (162 MHz, CDCl3) δ 32.5.[α] D 20 = -56.5 (c = 2.3, CHCl3). HRMS (ESI-MS) m / z calcd for C 29 H 26 O3P[M+H] +:453.1614, found: 453.1619. HPLC (IC, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 33.4 min (major), 37.6 min (minor).

[0248]

[0249] (3-(diphenylphosphoryl)-3-phenylprop-1-en-2-yl)boronic acid (6): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 5: 1) as eluent, 45.6 mg, 63% yield, 97% ee, white solid, m.p. 107-108 °C. 1 H NMR (400 MHz, CDC13) δ 7.85 - 7.80 (m, 2H), 7.59 - 7.47 (m, 5H), 7.41 - 7.28 (m, 7H), 7.21 - 7.11 (m, 3H), 5.76 (t, J = 2.3 Hz, 1H), 5.44 (t, J = 3.0 Hz, 1H), 4.35 (d, J = 8.8 Hz, 1H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 136.1 (d, J = 5.4 Hz), 132.9 (d, J = 12.2 Hz), 132.1 (dd, J = 17.4, 2.0 Hz), 131.4 (d, J = 28.5, 8.7 Hz), 130.7, 129.9 (d, J = 51.0 Hz), 129.4 (d, J = 7.0 Hz), 128.9, 128.6 (dd, J = 28.4, 16.6 Hz), 127.2, 57.3 (d, J = 64.1 Hz). 31 P NMR (162 MHz, CDC13) δ 37.8.[α] D 20 = -60.0 (c = 1.0, CHCl3). HRMS (ESI-MS) m / z calcd for C 21 H 21 BO3P[M+H] +363.1321, found: 363.1319. HPLC (AD-H, n-hexane / ethanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 15.0 min (minor), 20.9 min (major).

[0250]

[0251] (2-chloro-1-phenylallyl)diphenylphosphine oxide (7): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1 : 1) as eluent, 58.4 mg, 82% yield, 97% ee, white solid, m.p. 198-199 °C. 1 H NMR (600 MHz, CDC13) δ 7.97-7.93 (m, 2H), 7.58-7.52 (m, 3H), 7.37-7.32 (m, 3H), 7.27-7.25 (m, 2H), 7.23-7.17 (m, 5H), 6.20 (d, J = 1.2 Hz, 1H), 5.43 (br, 1H), 4.30 (d, J = 9.6 Hz, 1H). 13 C{ 1 H} NMR (151 MHz, CDC13) δ 137.5, 132.9 (d, J = 5.0 Hz), 132.4 (d, J = 10.0 Hz), 132.1 (d, J = 2.9 Hz), 131.8 (d, J = 14.0 Hz), 131.7 (d, J = 2.7 Hz), 131.4 (d, J = 8.9 Hz), 131.2 (d, J = 8.9 Hz), 130.2 (d, J = 5.1 Hz), 128.9 (d, J = 11.6 Hz), 128.4 (d, J = 1.5 Hz), 128.2 (d, J = 11.9 Hz), 127.9 (d, J = 2.3 Hz), 118.7 (d, J = 4.7 Hz), 56.1 (d, J = 62.4 Hz). 31 P NMR (162 MHz, CDC13) δ 30.8.[α] D 20 = -340.0 (c = 1.0, CHCl3). HRMS (ESI-MS) m / z calcd for C 21 H 19 ClOP [M+H] +353.0857, found: 353.0858. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 18.1 min (minor), 31.2 min (major).

[0252]

[0253] (2-bromo-1-phenylallyl)diphenylphosphine oxide (8): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1 : 1) as eluent, 78.7 mg, 99% yield, 99% ee, white solid, m.p. 212-213 °C. 1 H NMR (600 MHz, CDC13) δ 7.98-7.95 (m, 2H), 7.61-7.54 (m, 3H), 7.36-6.29 (m, 3H), 7.23-7.18 (m, 7H), 6.69 (br, 1H), 5.70 (d, J = 2.4 Hz, 1H), 4.39 (d, J = 9.0 Hz, 1H). 13 C{ 1 H} NMR (151 MHz, CDC13) δ 132.6 (d, J = 5.1 Hz), 132.3, 132.2 (d, J = 2.4 Hz), 131.7 (d, J = 2.3 Hz), 131.6 (d, J = 11.6 Hz), 131.3 (d, J = 8.8 Hz), 131.0 (d, J = 9.1 Hz), 130.1 (d, J = 4.9 Hz), 129.0 (d, J = 11.5 Hz), 128.4 (d, J = 1.4 Hz), 128.2 (d, J = 11.9 Hz), 127.9 (d, J = 1.8 Hz), 127.6, 123.4 (d, J = 4.8 Hz), 57.9 (d, J = 59.9 Hz). 31 P NMR (162 MHz, CDC13) δ 31.6.[α] D 20 = -185.0 (c = 2.0, CHCl3). HRMS (ESI-MS) m / z calcd for C 21 H 19 BrOP[M+H] +397.0351, found: 397.0352. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 17.1 min (minor), 30.5 min (major).

[0254]

[0255] diphenyl(1-phenylallyl)phosphine oxide (9): Purified by column chromatography on silica gel with petroleum ether / EtOAc (v / v = 1 : 1) as eluent, 41.3 mg, 65% yield, 86% ee, white solid, m.p. 180-181 °C. 1 H NMR (400 MHz, CDC13) δ 7.89 - 7.84 (m, 2H), 7.55 - 7.47 (m, 5H), 7.37 - 7.34 (m, 1H), 7.30 - 7.24 (m, 4H), 7.22 - 7.14 (m, 3H), 6.29 - 6.18 (m, 1H), 5.15 (dd, J = 10.0, 2.8 Hz, 1H), 5.04 (dd, J = 16.8, 4.0 Hz, 1H), 4.24 (t, J = 9.2 Hz, 1H). 13 C{ 1 H} NMR (101 MHz, CDC13) δ 135.5 (d, J = 6.2 Hz), 133.0 (d, J = 6.8 Hz), 131.7 (dd, J = 31.6, 8.6 Hz), 131.6 (d, J = 138.2 Hz), 131.5 (dd, J = 49.1, 2.7 Hz), 129.5 (d, J = 5.8 Hz), 128.6, 128.4 (dd, J = 33.6, 11.7 Hz), 127.2 (d, J = 2.0 Hz), 119.8 (d, J = 11.0 Hz), 52.9 (d, J = 65.1 Hz). 31 P NMR (162 MHz, CDC13) δ 31.8.[α] D 20 = -48.0 (c = 2.5, CHCl3). HRMS (ESI-MS) m / z calcd for C 21 H 20 OP[M+H] +: 319.1252, found: 319.1250. HPLC (AD-H, n-hexane / isopropanol = 90 / 10, flow rate = 1.0 mL / min, l = 220 nm) tR= 30.7 min (major), 38.2 min (minor).

[0256] Although the above embodiments have been described in detail, it should be understood that the detailed description is merely illustrative of the present embodiments, not completely describing all the embodiments. Other embodiments can be obtained according to the present embodiments without creativity, and these embodiments also belong to the protection scope of the present application.

Claims

1. An α-carbon chiral phosphine compound, characterized by, A compound having a structure of formula I: Formula I; In formula I, the R 1 is a C 1~8 alkyl group, a C 3~8 cycloalkyl group, a C 1~8 alkoxy group, , a phenyl group, , , , or ; R is C1-C6alkyl, phenyl, 2 C1-C6alkyl, phenyl, 1~4 C1-C6alkyl, phenyl, , , , , or thienyl.

2. The α-carbon chiral phosphine compound according to claim 1, wherein R 1 is phenyl, , , , , , , , , or ; R1is selected from the group consisting of 2 R1is selected from the group consisting of , , , , , , , , , , , or .

3. The α-carbon chiral phosphine compound according to claim 2, wherein The alpha-carbon chiral phosphine compound has any one of the following structures: 。 4. The process for producing an α-carbon chiral phosphine compound according to any one of claims 1 to 3, characterized by, The method comprises the following steps: In a protective gas atmosphere, an asymmetric boron protonation reaction of a stilbenyl phosphine oxide compound having a structure of formula II, pinacol borate, a copper(I) catalyst, a chiral ligand, an organic alkaline compound, a proton additive in a polar organic solvent to obtain the alpha-carbon chiral phosphine compound; the chiral ligand is a cyclic phosphine ligand (S, S)-Ph-BPE or a cyclic phosphine ligand (R, R)-Ph-BPE; the organic alkaline compound is sodium tert-butoxide; Formula II.

5. The preparation method according to claim 4, characterized in that, The copper(I) catalyst is one or more of CuCl, CuBr, CuI, CuOAc, CuTc and Cu(CH3CN)4PF6.

6. The preparation method according to claim 4, characterized in that, The asymmetric boron protonation reaction is carried out at a temperature of -30 to -60 °C.

7. The preparation method according to claim 4, characterized in that, The proton additive is methanol.

8. The preparation method according to claim 4, characterized in that, The molar ratio of the stilbenyl phosphine oxide compound having a structure of formula II to the pinacol borate is 1: (1-2); The molar ratio of the stilbenyl phosphine oxide compound having a structure of formula II to the copper(I) catalyst is 1:0.05; The molar ratio of the stilbenyl phosphine oxide compound having a structure of formula II to the chiral ligand is 1:0.06; The molar ratio of the stilbenyl phosphine oxide compound having a structure of formula II to the proton additive is 1:2; The molar ratio of the stilbenyl phosphine oxide compound having a structure of formula II to the organic alkaline compound is 1:0.

2.

9. The preparation method according to claim 6, characterized in that, The copper(I) catalyst is CuOAc; and the asymmetric boron protonation reaction is carried out at a temperature of -55 °C.

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